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Biomedical subjects

G McLean

Publications and source records attributed to G McLean.

At least 19 recordsLinked to original sources

Enhanced antitumour effect of liposomal daunorubicin using antibody-phospholipase C conjugates or fusion protein.

We have developed a new two-step method for targeting cytotoxic drugs to tumour cells. The method firstly involves the binding to tumour cells of antibody-phospholipase C immunoconjugates or fusion proteins. Further to washing or clearance of the immunoconjugates, liposomes are introduced which are specifically lysed at the tumour site by PLC to release their cytotoxic contents in the vicinity of the tumour cells. For two alternative human cell lines, a synergistic inhibition of cell proliferation was seen for combined treatment with a specific immunoconjugate and daunorubicin encapsulated liposomes. For tumour xenografts in mice, the combined treatment resulted in an inhibition of tumour growth although with no eradication of tumours at the doses used. The two-step antibody-PLC/liposome approach offers broad possibilities for the precise delivery of payloads of cytotoxic drugs to tumour sites.

Animals↗

Plasmodesmata: gateways for information transfer.

Intercellular communication in plants has evolved to occur via elongated cytoplasmic bridges, called plasmodesmata, that traverse the thick cell walls that surround plant cells. Historically, plasmodesmata have been assigned the mostly passive role of creating cytoplasmic continuity between plant cells enabling free transport of the wealth of small plant metabolites and growth hormones under 1 kDa. When it was discovered that plant viruses pirate plasmodesmata for movement of viral genomes during infection, it was proposed that viruses modified plasmodesmata for transport of very large molecules. Now, there is compelling evidence that plasmodesmata are inherently dynamic, rapidly altering their dimensions to increase their transport capabilities, upon contact with viral as well as developmentally important plant proteins. Further, the study of intercellular transport has prompted analyses of intracellular transport pathways, implicating the cytoskeleton as a major tracking system to plasmodesmata. Thus, plasmodesmata form a three-dimensional network of transportation channels and major checkpoints for information transfer. In the following, current knowledge about structure and function of these connective organelles, and about routing of molecules towards plasmodesmata, will be summarized.

Biological Transport↗

Deliberate overdose of uranium: toxicity and treatment.

A case is described of deliberate ingestion of 15 g of uranium acetate which resulted in acute renal failure requiring dialytic therapy for 2 weeks, refractory anaemia, rhabdomyolysis, myocarditis, liver dysfunction with a disproportionate coagulopathy and paralytic ileus. Despite significant elevations in plasma uranium levels, treatment with both calcium EDTA and calcium DTPA were ineffective in promoting uranium excretion. Six months later the initial significant renal impairment exists with a persistent incomplete Fanconi syndrome. Future options for management of this unusual cause of acute renal failure are discussed.

Acute Kidney Injury↗

The association between triple X and psychosis.

Two cases of psychotic illness in association with the karyotype triple X showed specific diagnostic and management problems as well as obstetric complications, EEG abnormalities, and lack of a family history of psychiatric disorder. Routine karyotyping during the investigation of psychosis is becoming relevant to psychiatric practice as research reports increasingly feature genetic and chromosome anomalies in association with schizophrenic psychoses.

Adult↗

Identification and characterization of the virion protein products of herpes simplex virus type 1 gene UL47.

We have identified two encoded proteins with an antiserum raised against a synthetic oligopeptide corresponding to amino acids 671 to 684 of the predicted protein product of gene UL47 of herpes simplex virus type 1 (HSV-1). They have apparent Mrs of 82,000 and 81,000 and are both major virion components located in the tegument. The 82/81K proteins were first detected in infected cells in minor amounts 6 h after infection at 37 degrees C but were later (from 10 h until 24 h after infection) present in large amounts. UL47 regulation was investigated using phosphonoacetic acid (PAA), an inhibitor of DNA synthesis: the amounts of the 82/81K protein synthesized were compared with those of 65KDBP, an early gene product, and 21K/22K, a true late gene product. The data showed that UL47 is regulated as a true late gene.

Amino Acid Sequence↗

Use of dried blood on filter paper in the ELISA for Brucella abortus.

An ELISA for Brucella abortus antibody detection using blood collected on filter paper is described. The method gave similar results to the complement fixation test. The signal-noise ratio was good. The system offers considerable advantages when transport of serum samples to the laboratory causes problems.

Animals↗

A molecular approach to immunoscintigraphy: a study of the T-antigen conformation on the surface of tumors.

The role of glycoconjugates in tumor cell differentiation has been well documented. We have examined the expression of the two anomers of the Thomsen-Friedenreich antigen on the surface of human, canine and murine tumor cell membranes both in vitro and in vivo. This has been accomplished through the synthesis of the disaccharide terminal residues in both alpha and beta configuration. Both entities were used to generate murine monoclonal antibodies which recognized the carbohydrate determinants. The determination of fine specificities of these antibodies was effected by means of cellular uptake, immunohistopathology and immunoscintigraphy. Examination of pathological specimens of human and canine tumor tissue indicated that the expressed antigen was in the beta configuration. More than 89% of all human carcinomas tested expressed the antigen in the above anomeric form. The combination of synthetic antigens and monoclonal antibodies raised specifically against them provide us with invaluable tools for the study of tumor marker expression in humans and their respective animal tumor models.

Animals↗

Central venous access with occlusive superior central venous thrombosis.

Thrombotic occlusion of the entire superior central venous system is a rare complication of central venous catheterization. Three patients are presented with complete occlusion of the superior vena cava secondary to prolonged central venous catheterization. Thrombotic occlusion of the superior vena cava precludes central venous access by conventional techniques. Thoracotomy with direct catheterization of the right atrium and inferior vena cava cannulation represent alternative approaches but may be associated with significant morbidity. The present report describes a unique combined angiographic/operative technique designed to obtain central venous access with low morbidity in patients with occlusive thrombosis of the superior central venous system.

Adult↗

Coronary vein aneurysm presenting as pancreatic pseudocyst.

This report, the first known published account, describes an unusual case of suspected pancreatic pseudocyst diagnosed by ultrasonography which at operation and subsequent arteriography was found to be a coronary vein aneurysm. Owing to the nonspecificity of ultrasonographic detection of vascular anomalies and neoplasms, arteriography is recommended when surgery is planned.

Aneurysm↗

Continuous ambulatory peritoneal dialysis.

Continuous ambulatory peritoneal dialysis is a portable wearable method of treatment for patients with end-stage renal failure. We describe our experience with 42 patients treated by this technique. Continuous ambulatory peritoneal dialysis provided satisfactory biochemical control of uraemia. Major problems encountered were peritonitis, catheter malfunction and the effects of raised intra-abdominal pressure. Patient motivation, compliance and good family support help predict those patients in whom the technique will be successful.

Abdomen↗

Angiography of skeletal disease.

Recent technical advances have produced two new applications for arteriography in the management of patients with bone tumors: angiography can be used in the planning of free vascularized grafts and in interventional radiologic therapy for bone tumors. Also discussed is the role of angiography in trauma.

Angiography↗

Treatment of acute peripheral arterial and graft thromboses with low-dose streptokinase.

Seventeen patients with acute peripheral arterial or graft occlusion were treated with local low-dose intra-arterial streptokinase. The series includes eight patients with native vessel occlusion, six patients with vein graft occlusion, two patients with prosthetic graft occlusion, and one patient with renal allograft artery occlusion. The duration of occlusion prior to streptokinase therapy varied from 2 hours to 5 weeks. The treatment was successful in 14 of the 17 instances. In conjunction with the successful thrombolytic therapy, percutaneous transluminal angioplasty was performed subsequently in 10 of the patients and reconstructive surgery in three. One major and five minor hemorrhagic complications occurred and were considered to be secondary to the streptokinase therapy. In follow-up of up to 9 months, 11 of the 14 successfully treated patients continued to have a good result, without any indication of recurrent arterial occlusion. Two patients have died of causes unrelated to thrombolytic therapy and one patient required bypass grafting for recurrent thrombosis. None of the successfully treated patients lost a limb. Of the three patients in whom thrombolysis was unsuccessful, two required amputation. Local intra-arterial low-dose streptokinase appears to be a promising alternative to immediate operative treatment in carefully selected cases of arterial occlusion. Definitive treatment of the underlying cause of the thrombus usually is required and changes of success may be enhanced by the thrombolytic therapy.

Adult↗