Comparison of morphine and morphine with ketamine for postoperative analgesia

In addition to the patient's history and a thorough clinical investigation, magnetic resonance imaging (MRI) of the temporomandibular joint (TMJ) has been introduced to complete the findings for the diagnosis of internal derangement of the TMJ. However, 'dynamic information' is desirable to help us to understand the mechanism of internal derangement. This information is given for example by electronic axiography recording systems. The lack of any ability to assess joint function dynamically in MRI is a point of criticism. Using a computer-driven pseudodynamic MRI system (CINE mode) 'dynamic information' should be now available. In this investigation 21 patients with TMJ disorders were examined using both conventional static MRI and CINE mode. For the diagnosis of an anterior displaced disc with or without reduction in 18 cases (86%) it was only necessary to consider two static MRIs: a closed mouth position and a maximal open mouth position. Comparison showed there was no advantage in using CINE mode. Contrast and resolution of the static MRIs were shown to be better and so additional findings such as joint effusion and disc deformation could be diagnosed on static MRIs with greater certainty. Only in three (14%) cases was the dynamic information from CINE mode useful for the diagnosis of the displacement of the disc.     

Diagnosis of ectoparasitism

A vacuum cleaner fitted with an in-line filter was used to collect samples from suspected cases of ectoparasitic infestation in animals. Filter samples, including hair, were hydrolyzed in hot potassium hydroxide, and the residue was concentrated by flotation in concentrated sugar and then examined under a microscope. The 206 animals examined yielded fleas, flea feces, forage mites, Cheyletiella, Sarcoptes, Chorioptes, Psoroptes, Otodectes, Demodex and Damalinia spp. The sensitivity of this technique in the diagnosis of ectoparasites was better than that of conventional skin scrapings or direct observation.     

Molecular genetic diagnosis of von Hippel-Lindau disease in familial phaeochromocytoma

Inherited predisposition to phaeochromocytoma is seen in multiple endocrine neoplasia type 2 syndromes, von Hippel-Lindau (VHL) disease, and neuro-fibromatosis type 1. In addition familial phaeochromocytoma alone has been reported. To investigate the genetic basis for familial phaeochromocytoma alone, we screened three affected kindreds for mutations in the RET proto-oncogene and the VHL tumour suppressor gene. We did not detect MEN 2 associated RET mutations in any family, but missense VHL gene mutations (V155L and R238W) were identified in two kindreds with no clinical evidence of VHL disease. Patients with familial, multiple, or early onset phaeochromocytoma should be investigated for germline VHL and RET gene mutations as the molecular diagnosis of multisystem familial cancer syndromes enables appropriate counselling and screening to be provided.     

Retention of oncogenicity by a Marek's disease virus mutant lacking six unique short region genes

We previously reported the construction of Marek's disease virus (MDV) strains having mutations in various genes that map to the unique short (US) region of the viral genome (J.L. Cantello, A.S. Anderson, A. Francesconi, and R.W. Morgan, J. Virol. 65:1584-1588, 1991; M.S. Parcells, A.S. Anderson, and R.W. Morgan, Virus Genes 9:5-13, 1994; M.S. Parcells, A.S. Anderson, and R.W. Morgan, J. Virol. 68:8239-8253, 1994). These strains were constructed by using a high-passage-level serotype 1 MDV strain which grew well in chicken embryo fibroblasts. Despite the growth of the parent and mutant viruses in cell culture, in vivo studies were limited by poor growth of these strains in chickens. One of the mutants studied lacked 4.5 kbp of US region DNA and contained the lacZ gene of Escherichia coli inserted at the site of the deletion. The deletion removed MDV homologs to the US1, US2, and US10 genes of herpes simplex virus type 1 as well as three MDV-specific open reading frames. We now report the construction of a mutant MDV containing a similar deletion in the US region of the highly oncogenic RB1B strain. This mutant, RB1B delta 4.5lac, had a growth impairment in established chicken embryo fibroblasts similar to that described previously for MDVs lacking a functional US1 gene. In chickens, RB1B delta 4.5lac showed decreased early cytolytic infection, mortality, tumor incidence, and horizontal transmission. Several lymphoblastoid cell lines were established from RB1B delta 4.5lac-induced tumors, and virus reactivated from these cell lines was LacZ+. These results indicate that the deleted genes are nonessential for the transformation of chicken T cells or for the establishment and maintenance of latency. On the basis of the growth impairment observed for RB1B delta 4.5lac in cell culture and in vivo, we conclude that deletion of these genes affects the lytic replication of MDV. This is the first MDV mutant constructed in the RB1B oncogenic strain, and the methodology described herein provides for the direct examination of MDV-encoded determinants of oncogenicity.     

IL-1 beta and TNF alpha modulate delta 9-tetrahydrocannabinol-induced catalepsy in mice

The role of the proinflammatory cytokines interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF alpha) in THC-induced catalepsy in mice was examined. Recombinant IL-1 beta (400 ng/mouse, IV) and TNF alpha (500 ng/mouse, IV) were effective in potentiating the cataleptic effect of low-dose THC (10 micrograms/mouse, IV). Recombinant IL-1 alpha and IL-6 did not potentiate catalepsy at any dose tested. Anti-IL-1 beta and anti-TNF alpha antibodies were effective in attenuating high-dose (75 micrograms/mouse) THC-induced catalepsy. Antibodies to IL-1 alpha and IL-6 had no effect on catalepsy. Early onset catalepsy (10 min postinjection) was potentiated by exogenous recombinant IL-1 beta and TNF alpha but only later catalepsy (2 h postinjection) was attenuated by antibodies to endogenous IL-1 beta or TNF alpha. This divergence of the cytokine effect suggests that these substances regulate, by different mechanisms, the early and late THC-induced cataleptic response.     

Oligomerization of epidermal growth factor receptors on A431 cells studied by time-resolved fluorescence imaging microscopy. A stereochemical model for tyrosine kinase receptor activation

The aggregation states of the epidermal growth factor receptor (EGFR) on single A431 human epidermoid carcinoma cells were assessed with two new techniques for determining fluorescence resonance energy transfer: donor photobleaching fluorescence resonance energy transfer (pbFRET) microscopy and fluorescence lifetime imaging microscopy (FLIM). Fluorescein-(donor) and rhodamine-(acceptor) labeled EGF were bound to the cells and the extent of oligomerization was monitored by the spatially resolved FRET efficiency as a function of the donor/acceptor ratio and treatment conditions. An average FRET efficiency of 5% was determined after a low temperature (4 degrees C) incubation with the fluorescent EGF analogs for 40 min. A subsequent elevation of the temperature for 5 min caused a substantial increase of the average FRET efficiency to 14% at 20 degrees C and 31% at 37 degrees C. In the context of a two-state (monomer/dimer) model for the EGFR, these FRET efficiencies were consistent with minimal average receptor dimerizations of 13, 36, and 69% at 4, 20, and 37 degrees C, respectively. A431 cells were pretreated with the monoclonal antibody mAb 2E9 that specifically blocks EGF binding to the predominant population of low affinity EGFR (15). The average FRET efficiency increased dramatically to 28% at 4 degrees C, indicative of a minimal receptor dimerization of 65% for the subpopulation of high affinity receptors. These results are in accordance with prior studies indicating that binding of EGF leads to a fast and temperature-dependent microclustering of EGFR, but suggest in addition that the high affinity functional subclass of receptors on quiescent A431 cells are present in a predimerized or oligomerized state. We propose that the transmission of the external ligand-binding signal to the cytoplasmic domain is effected by a concerted relative rotational rearrangement of the monomeric units comprising the dimeric receptor, thereby potentiating a mutual activation of the tyrosine kinase domains.