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Biomedical subjects

M A Buchanan

Publications and source records attributed to M A Buchanan.

4 recordsLinked to original sources

Oncogenes in thyroid cancer.

There have been significant advances in our understanding of carcinogenesis at the molecular level over the last 25 years. Oncogenes are of major interest as part of our search for knowledge surrounding the aetiology of cancer. There are several oncogenes associated with thyroid cancer. Detailed investigation of the nature and function of these tumour genes has provided important insights into both the tumour biology and the complex biochemical pathways of normal cellular functioning. Our knowledge of oncogene biology offers the hope of better diagnostic, therapeutic and prognostic modalities in our fight against this and other common cancers. Development of specific thyroid tumour markers and gene therapy is now a realistic prospect to supplement our present armamentarium of surgery and radiotherapy. This review aims to outline the pertinent information gained so far from studies of these oncogenes and provides both clinical relevance and fuel for further interest amongst the ENT thyroid community in this exciting area of research.

Carcinoma, Medullary↗

Primary defects in the lens underlie complex anterior segment abnormalities of the Pax6 heterozygous eye.

We describe lens defects in heterozygous small eye mice, and autonomous deficiencies of Pax6(+/-) cells in the developing lens of Pax6(+/+) <--> Pax6(+/-) chimeras. Two separate defects of the lens were identified by analyzing the distribution of heterozygous cells in chimeras: Pax6(+/-) cells are less readily incorporated into the lens placode than wild type, and those that are incorporated into the lens are not maintained efficiently in the proliferating lens epithelium. The lens of chimeric eyes is, therefore, predominantly wild type from embryonic day 16.5 onwards, whereas heterozygous cells contribute normally to all other eye tissues. Eye size and defects of the iris and cornea are corrected in fetal and adult chimeras with up to 80% mutant cells. Therefore, these aspects of the phenotype may be secondary consequences of primary defects in the lens, which has clinical relevance for the human aniridia (PAX6(+/-)) phenotype.

Animals↗

Thyroid auto-antibodies, lymphocytic infiltration and the development of post-operative hypothyroidism following hemithyroidectomy for non-toxic nodular goitre.

BACKGROUND: Auto-immune thyroiditis, associated with detectable thyroid auto-antibodies (TAAs) and lymphocytic infiltration into the gland, is known to be associated with progressive development of hypothyroidism. This study examines those patients who required surgical treatment of non-toxic nodular goitre by hemithyroidectomy to determine whether the presence of TAAs in the circulation and/or lymphocytic infiltration of the gland resulted in a significant degree of post-operative hypothyroidism. METHOD: This was a prospective study, with data collected retrospectively. All patients operated on for thyroid disease in the unit over a 5-year period were documented, and those patients treated by hemithyroidectomy for non-toxic nodular goitre formed the study group. TAAs were measured, histology re-examined and patients followed up for at least 2 years to detect clinical or sub-clinical hypothyroidism. RESULTS: Of the 158 patients who comprised the study group, 38 (24.1%) developed hypothyroidism. Forty-one (25.9%) had circulating levels of TAAs, 31 of these (75.6%) having high levels. Of these 41 patients, 22 (53.7%) became hypothyroid. Twenty (64.5%) of the 31 patients with high levels of TAAs required post-operative thyroxine. Of the remaining 117 patients with no detectable TAAs, only 16 (13.7%) became hypothyroid. CONCLUSION: All patients requiring treatment by hemithyroidectomy should have circulating TAA measurements carried out pre-operatively. If positive, they should be followed up indefinitely because of the strong possibility (P < 0.001) of the development of hypothyroidism.

Adolescent↗

Autocrine growth and progression of murine X-ray-induced T cell lymphomas.

Primary tumors of X-ray-induced murine T cell lymphomas comprise autocrine, growth factor-dependent cells. We have grown cell lines from primary X-ray-induced thymic lymphomas (PXTLs) under conditions which minimize the progression of the cells from factor dependence to factor independence. All (22) PXTL lines grown secrete a growth factor which supports their own growth and which we will call lymphoma growth factor LGF. LGF-dependent cells are non-tumorigenic or poorly tumorigenic, do not clone in soft agar, have no detectable rearrangements in the c-myc or Pim-1 region and possess near diploid or pseudodiploid karyotypes without evidence for trisomy of chromosomes nos. 15 or 17. PXTL-secreted LGF has no interleukin 1, 2, or 3 activity nor do LGF-secreting cells synthesize detectable IL-1, -2, or -3 mRNA. LGF contains no detectable interferon or GM-CSF activity in specific bioassays. Purified EGF, TGF beta, and interleukin preparations are inactive on LGF-dependent PXTL cells. Thus LGF appears to be a new growth factor that is required for the proliferation of non-progressed T lymphoma cells. Upon progression PXTL cells become growth factor independent, are highly tumorigenic in vivo, clone in soft agar, and assume a near triploid karyotype containing numerous chromosomal aberrations. Thus in X-ray-induced lymphomagenesis an autocrine, LGF-dependent phase precedes the progressed phase characterized by rearrangements in the myc and/or Pim-1 regions as well as by many chromosomal aberrations visible in the karyotype.

Animals↗