Antinociceptive Effects of Morphine Were Different Between Experimental and Genetic Diabetes

This study was designed to investigate the effect of morphine on formalin-induced nociceptive responses in streptozotocin (STZ) induced-diabetic mice, noninsulin-dependent genetically diabetic db/db mice and their respective controls (ddY and +/+). In nondiabetic (ddY and +/+) mice, morphine (1–10 mg/kg, PO) dose dependently attenuated the biphasic nociceptive responses induced by SC injection of formalin to the hindpaw, demonstrating equipotency on both the first and second phases. Para-chlorophenylalanine (800 mg/kg × 2, PO) and pindolol (1 mg/kg, IP) reduced the effect of morphine on the first phase, sulpiride (10 mg/kg, IP) abolished the effect on both phases, while ketanserin (1 mg/kg, IP) had no effect. In STZ (200 mg/kg, IP)-diabetic mice, morphine weakly attenuated the nociception in comparison to control ddY mice, whereas it had comparable effects in both the first and second phases of control +/+ mice and db/db mice. The serotonergic agonist, meta-chlorophenylpiperazine (0.32–3.2 mg/kg, PO), dose dependently attenuated the biphasic nociceptive responses to formalin in both phases of diabetic mice; however, FR64822, a dopaminergic compound (0.1–10 mg/kg, PO), had little effect. We speculate that activation of both dopaminergic (DA)- and serotonergic-mediated mechanisms are potentially responsible for the effect of morphine on the first phase, while the DA-mediated effect is involved in the second phase. The DA-mediated mechanism, but not the serotonin-mediated one, appears to be altered in both STZ-diabetic and db/db mice. These results suggest that the attenuated effects of morphine might be due to a dopaminergic dysfunction in STZ mice, and that there might be other mechanisms compensating for this attenuation of dopaminergic function in db/db mice.     

Keratinocyte-derived Cytokines and UVB-Induced Immunosuppression

Ultraviolet radiation (UVB) in sunlight is known to have multiple effects on the immune system. Evidence suggests that UVB-induced immunosuppression is mediated in part by immunosuppressive and immunoregulatory cytokines. Our studies have utilized gene-targeted mutant mice to determine key molecular requirements essential for the development of UVB-induced immunosuppression. Preliminary results from our laboratory suggest that TNF-α plays a regulatory role in contact hypersensitivity, but is not a crucial factor for UVB-induced immunosuppression, and that multiple factors are involved in the induction of UVB mediated immunosuppression.     

Contribution of tumor necrosis factor to the lethality of mice with endotoxin shock presensitized by serum from tumor-bearing mice

Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 115, No. 1, pp. 57–59, January, 1993.     

Mixed dysembryoplastic neuroepithelial tumor and ganglioglioma

We report a case of a 15-year-old girl with new onset seizures, who had a mixed dysembryoplastic neuroepithelial tumor (DNT) and ganglioglioma of the right parieto-occipital lobe. The tumor appeared well demarcated and exhibited a low T1 and a high T2 signal on magnetic resonance imaging. Architecturally it was in large part intracortical and multinodular, but also featured a leptomeningeal component. The former corresponded to DNT, a proliferation of oligodendroglia-like cells (OLCs) arranged in nodules, as well as comprising a diffuse internodular element featuring “floating neurons” in a mucoid matrix. The leptomeningeal portion of the lesion was a ganglioglioma consisting of large neurons and astrocytes in association with marked desmoplasia. Spacially, the two components abutted one another but appeared distinct. Immunohistochemistry showed the neurons of the ganglioglioma to be positive for class III β-tubulin, synaptophysin, and chromogranin A, whereas the astrocytic cells stained only for glial fibrillary acidic protein. Most OLCs in the DNT were positive for S-100 protein. This apparently mixed lesion suggests that a close histogenetic relationship exists between DNT and ganglioglioma. We postulate that the pluripotential progenitor cells residing in the subpial granular layer may have given rise to the cortical DNT and to the leptomeningeal ganglioglioma. To our knowledge, this is the first detailed histological, immunochemical and ultrastructural report of a mixed DNT and ganglioglioma. Received: 11 August 1997 / Revised, accepted: 24 November 1997     

Intra-abdominal desmoplastic small cell tumor presenting as an acute abdomen after trauma

The intraperitoneal mass most commonly encountered after blunt abdominal truama is a hematoma. However, one must also consider unusual bulky tumors that can have imaging characteristics similar to those of hematoma. The most typical of these neoplasms is lymphoma, but a desmoplastic small cell tumor also may be observed. The presentation and imaging findings of a desmoplastic small tumor are described.     

Metastatic Behavior and Tumorigenicity of a Human Melanoma Cell Line (MM-RU) after Injection into Nude Mice

The ability of the human amelanotic melanoma cell line MM-RU to produce experimental metastases and to grow tumors at subcutaneous inoculation sites in 4-week-old nude mice was examined. After i.v. inoculation of 10⁶ cells, all injected mice (n=21) developed consistent numbers of metastatic pulmonary colonies within 32 days. The coefficients of variation for the number of colonies were between 17%–23% in three independent experiments. Survival time after i.v. inoculation was 63 ± 7 days (mean ± SD) (n=20). Within 20 days, subcutaneous inoculation of 5 × 10⁶ cells resulted in tumor growths of 13 ± 3 mm (mean ± SD) at the inoculation sites in all nude mice (n=12). The MM-RU cell line seems to be a simple, fast vehicle for testing the effect of melanoma growth modulators on experimental pulmonary metastases as well as on subcutaneously growing melanoma.     

The human desmin gene: A specific regulatory programme in skeletal muscle both in vitro and in transgenic mice

Desmin synthesis is restricted to cardiac, skeletal and smooth muscles. In several familial myopathies involving fibre disorganization, filamentous aggregation of desmin has been characterized. During the development of the mouse embryo, desmin is one of the first muscle proteins detected in both the heart and the somites. To identify the DNA sequences involved in the regulation of desmin gene expression a 4.5 kb 5′-flanking region of the human desmin gene has been isolated. Different mutants were used to characterize specific enhancers in vitro and in vivo. The results obtained with transgenic mice provide evidence that the 1 kb cis-regulatory sequences, functional in skeletal muscle cells in vitro, confer specific developmental control for skeletal muscles. Furthermore, distinct programmes for cardiac and skeletal muscle-specific expression of the desmin gene are revealed.     

肺肿瘤细胞雌激素、孕激素和凝集素受体的组化研究

用酶联亲合组化法对46例肺肿瘤细胞进行了雌激素受体(ER)和孕激素受体(PR)检测。同时测定14例肺瘤肿患者血清雌二醇(E_2)浓度。结果表明:肺肿瘤 ER 阳性率为36.9%,PR 阳性率为13.0%。阳性率与性别、病理类型及血浆 E_2浓度无关。认为肺癌的发生发展可能与雌激素有依赖关系,提示内分泌疗法可能会成为原发肺肿瘤的一种治疗手段。另用 ABC 法对上述46例肺肿瘤中的29例进行了花生凝集素受体(PNA-R)和麦胚凝集素受体(WGA-R)的检测,PNA-R 在腺癌大都为顶浆型分布,鳞癌和透明细胞癌则多为胞膜型分布。结果提示 PNA-R 是肺癌分化过程中的一种标志,对肺癌分型、预后判断有一定协助作用。同时将29例肺肿瘤 PNA-R 与 ER 状况作对比研究,探讨了二者之间的相关性及可能的发生机制。     

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.     

Comparison of local tumor recurrence following excision with the CO2 laser, Nd:YAG laser, and Argon Beam Coagulator

This study compares the incidence of local tumor recurrence following primary excision with the CO2 laser, Nd:YAG laser (contact), Argon Beam Coagulator, or electrocautery. One hundred eight Fisher 344 rats with R3230AC mammary tumors (1.6 +/- 0.04 [SD] cm diameter) were used. All animals were randomized into groups of similar tumor size. In groups C and CS, excision was performed with a Sharplan 1060 CO2 laser (TEMoo, 25 W, continuous wave [CW], 0.2-mm spot size). Wounds in group CS were "sterilized" (0.5-mm spot size, 25 W, CW) by gently heating the wound without causing blanching or charring. In group N, a 0.4-mm contact Laser Blade and a Cooper 8000 Nd:YAG laser at 20 W CW was used. In groups SA1 and SA2, tumors were excised with the scalpel, and hemostasis and wound "sterilization" were accomplished with the Bard System 6000 Argon Beam Coagulator (ABC) at 40 W and 4 liters/min argon gas flow in SA1 and 12 liters/min in SA2. In group E, excision was accomplished at 40 W blend mode, 10 W spray mode. In group EA, excision was accomplished at 60 W cutting current, and hemostasis was achieved with the ABC. The animals were examined for evidence of recurrence for 34 days postoperatively. Mortalities were excluded from analysis. The incidence of recurrence was 11/14 (79%) in C, 6/16 (38%) in CS, 10/14 (71%) in SA1, 6/13 (46%) in SA2, 6/15 (40%) in N, 7/10 (70%) in EA, and 3/15 (20%) in E. Group E is statistically different (P less than .01) from groups EA, C, and SA1. Group C was different (P less than .01) from groups E, CS, and N. These results demonstrate an inverse relationship between tumor recurrence and local thermal effects at the surgical site. The ABC did not increase tumor recurrence. Contact YAG surgery was similar to CO2 laser excision and "sterilization." An attempt to study the influence of gas flow and pressure on local tumor recurrence and metastases should be made.