Establishment and characterization of a panel of human lung cancer cell lines.

The establishment and characterization of 11 human lung cancer cell lines are described in this article. Nine of these cell lines were established over a 5-year period, from 1983 to 1988, from patients treated at the Kingston Regional Cancer Centre. These include eight definite or probable small cell lung cancer (SCLC) lines and one adenocarcinoma line. In addition, two other SCLC cell lines were characterized. All of the lines have been in continuous culture for more than 2 years. The clinical histories of the patients from whom the cell lines were derived are outlined here. Several features of the cell lines are presented, including the following: (1) a comparison of the histologic features of the cell lines with the original biopsy specimens; (2) the expression of various markers, including cytokeratin, carcinoembryonic antigen, calcitonin, and neuron-specific enolase; (3) activities of the enzymes l-dopa decarboxylase and the brain isoenzyme of creatine kinase; (4) growth characteristics; (5) cloning efficiency in soft agar; (6) tumorigenicity in nude mice; and (7) cytogenetic studies. These cell lines, obtained directly from patients with a spectrum of drug-sensitive and drug-resistant tumors, will be valuable in vitro models of sensitivity and resistance to chemotherapy in lung cancer.     

Fracture of polyethylene tibial component in a total knee replacement. A case report

Aseptic loosening is the most common mode of failure for total knee replacements. Component breakage is rare, usually attributable to errors of design or manufacture. A case is presented in which rotational malplacement of the femoral component resulted in accelerated wear and eventual fracture of the polyethylene tibial component.     

PCR-SSO typing for DR4-Dw subtypes: application to unrelated bone marrow transplant donor selection

Thirty-seven DR4-positive patient-unrelated bone marrow donor pairs previously DR/DQ restriction fragment length polymorphism (RFLP) typed and tested in mixed lymphocyte culture (MLC), have been DR4-Dw subtyped retrospectively using sequence specific oligonucleotide probes. We found that DR4-Dw subtyping substantially increased the accuracy of pre-MLC matching and could potentially accelerate donor searches by avoiding unnecessary MLC tests on Dw-mismatched donors.     

Sensitisation to Swine Leukocyte Antigens in Patients with Broadly Reactive HLA Specific Antibodies

We have previously shown that IgG HLA specific antibodies in the sera of highly sensitised patients awaiting renal transplantation can cross-react with swine leukocyte antigens (SLA). In this study we determined the frequency of patient serum IgG HLA specific antibody binding to a porcine lymphocyte panel and the likelihood of locating a cross-match negative pig donor for sensitised patients. Serum samples (n = 82) were obtained from 35 sensitised [current IgG panel reactive antibodies (PRA) > 10%] and seven nonsensitised patients awaiting renal transplantation at Addenbrooke's Hospital, Cambridge, UK. Fifty sera had IgG HLA specific PRA of 11-84%, 20 had IgG PRA of >84% and 12 had 0% PRA (negative controls). Sera were absorbed with porcine erythrocytes to remove xenoreactive natural antibodies and tested for cross-reactive IgG HLA specific antibody binding by flow cytometry against a panel of porcine lymphocytes obtained from 23 human decay accelerating factor (hDAF) transgenic pigs. A total of 1,884 cross-match combinations were tested and 369 (20%) gave a positive porcine lymphocyte cross-match. For sera from sensitised patients with IgG PRA (11-64%), only 6 of 805 (0.75%) cross-match tests were positive. In contrast, for sera from patients with high IgG PRA (>64%), 363 of 805 (45%) cross-match tests were positive (p < 0.0001). There was no difference in the frequency of positive cross-matches between patient sera with IgG PRA 65-84% and highly sensitised patient sera with IgG PRA 85-100% [156/345 (45%) vs. 207/460 (45%)]. This study demonstrates that only patient sera with broadly reactive IgG HLA specific PRA (>64%) cross-react with porcine lymphocytes. If future clinical trials of xenotransplantation are undertaken, it may be of value to select a cross-match-negative pig organ donor for such patients.     

Use of gadolinium chelates in MR imaging of the spine

Spinal disease can be divided into intramedullary, extramedullary-intradural, and extradural compartments. In the cord (intramedullary compartment), gadolinium chelates are useful to diagnose primary and metastatic tumors, inflammation, and demyelination, and to evaluate syringomyelia when a Chiari I malformation is not present. In the extra-medulullary-intradural compartment, gadolinium chelates are useful for the diagnosis of drop metastases, meningiomas, and schwannomas. In the extradural compartment, gadolinium chelates are most useful to distinguish recurrent disc herniation from epidural fibrosis in the postoperative back and may be useful to diagnosis the soft tissue component of osseous metastases.     

OUTCOME AFTER FRACTURES OF THE FEMUR IN PAGET'S DISEASE

We reviewed ninety-three patients who had one hundred and seven complete fractures of the femur between them and were treated over a twenty-five year period in Western Australia and South Australia. Operative surgical management of complete fractures in the middle and distal thirds was usually successful. In contrast, fractures proximal to the middle third were regularly associated with non-union, implant failure and requirement for revision surgery. In view of this significant difference in outcome after fracture of the pagetic femur in different sites, a comprehensive surgical management strategy is recommended in order to avoid complications.     

Novel antagonists of the 5-HT3 receptor. Synthesis and structure-activity relationships of (2-alkoxybenzoyl)ureas.

A series of benzoylureas derived from bicycle amines were prepared and evaluated for 5-HT3 antagonist activity on the rat isolated vagus nerve. From among these compounds, those analogues which were ortho substituted by an alkoxy group on the benzoyl function were shown to be potent 5-HT3 antagonists with similar or greater potency than the standard agent ondansetron. NMR and X-ray crystallography studies showed these o-alkoxy compounds to exist as a planar, hydrogen-bonded, tricyclic ring system. In molecular modeling studies on endo-N-[[(8-methyl-8-azabicyclo[3.2.1]octan-3-yl-amino] carbonyl]-2-(cyclopropylmethoxy)benzamide (30) the central hydrogen-bonded ring was able to mimic an aromatic ring present in previously reported 5-HT3 antagonists.