Abstract. The serum T 3 to T 4 ratio is a useful indicator for differentiating destruction-induced thyrotoxicosis from Graves' thyrotoxicosis. However, the usefulness of the serum free T 3 (FT 3 ) to free T 4 (FT 4 ) ratio is controversial. We therefore systematically evaluated the usefulness of this ratio, based on measurements made using two widely available commercial kits in two hospitals. Eighty-two untreated patients with thyrotoxicosis (48 patients with Graves' disease and 34 patients with painless thyroiditis) were examined in Kuma Hospital, and 218 patients (126 with Graves' disease and 92 with painless thyroiditis) and 66 normal controls were examined in Ito Hospital. The FT 3 and FT 4 values, as well as the FT 3 / FT 4 ratios, were significantly higher in the patients with Graves' disease than in those with painless thyroiditis in both hospitals, but considerable overlap between the two disorders was observed. Receiver operating characteristic (ROC) curves for the FT 3 and FT 4 values and the FT 3 /FT 4 ratios of patients with Graves' disease and those with painless thyroiditis seen in both hospitals were prepared, and the area under the curves (AUC), the cut-off points for discriminating Graves' disease from painless thyroiditis, the sensitivity, and the specificity were calculated. AUC and sensitivity of the FT 3 /FT 4 ratio were smaller than those of FT 3 and FT 4 in both hospitals. The patients treated at Ito hospital were then divided into 4 groups according to their FT 4 levels (A: £2.3, B: >2.3~£3.9, C: 3.9~£5.4, D: >5.4 ng/dl), and the AUC, cutoff points, sensitivity, and specificity of the FT 3 /FT 4 ratios were calculated. The AUC and sensitivity of each group increased with the FT 4 levels (AUC: 57.8%, 72.1%, 91.1%, and 93.4%, respectively; sensitivity: 62.6%, 50.0%, 77.8%, and 97.0%, respectively). The means ± SE of the FT 3 /FT 4 ratio in the Graves' disease groups were 3.1 ± 0.22, 3.1 ± 0.09, 3.2 ± 0.06, and 3.1 ± 0.07, respectively, versus 2.9 ± 0.1, 2.6 ± 0.07, 2.5 ± 0.12, and 2.3 ± 0.15, respectively, in the painless thyroiditis groups. In the painless thyroiditis patients, the difference in the FT 3 /FT 4 ratio between group A and group D was significant (p<0.05). Thus, the FT 3 /FT 4 ratio in patients with Graves' disease likely remains unchanged as the FT 4 level rises, whereas this ratio decreases as the FT 4 level rises in patients with painless thyroiditis. In conclusion, the FT 3 /FT 4 ratios of patients with painless thyroiditis overlapped with those of patients with Graves' disease. However, this ratio was useful for differentiating between these two disorders when the FT 4 values were high.

In non-Hodgkin's lymphoma (NHL), the majority of translocations involve the immunoglobulin heavy chain gene (IGH) locus, while a few involve the immunoglobulin light chain gene (IGL) locus, consisting of the kappa light chain gene (IGkappa) and the lambda light chain gene (IGlambda). Although many reports have dealt with the translocation and/or amplification of IGH in NHL, only a few have identified IGL translocations. To identify cytogenetic abnormalities and the partner chromosomes of IGL translocations in NHL, we performed dual-colour fluorescence in situ hybridisation (DC-FISH) and spectral karyotyping (SKY) in seven NHL cell lines and 40 patients with NHL. We detected IGL translocations in two cell lines and nine patients: four patients with diffuse large B-cell lymphoma, three with follicular lymphoma, one with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue and one with mantle cell lymphoma. Five distinct partners of IGlambda translocation were identified by SKY analysis: 3q27 in three patients, and 1p13, 6p25, 17p11.2 and 17q21 in one patient each. Three cases featured double translocations of IGH and IGL. These findings warrant the identification of novel genes 1p13, 6p25, 17p11.2 and 17q21.

Protein tyrosine kinases (PTKs) play a role in regulating the growth and differentiated functions of thyroid cells and are probably involved in tumorigenesis of papillary-type thyroid carcinoma. To better understand the roles of PTKs in the physiology and pathophysiology of the thyroid, we analyzed the expression profile of receptor-type PTKs in normal human thyroid tissues. Highly conserved regions in the catalytic domains of receptor-type PTKs were amplified by RT-PCR using degenerate oligonucleotide primers. Nucleotide sequencing of about 100 clones identified 21 PTKs, including 16 receptor type and 5 nonreceptor type; no novel PTK was identified. Insulin-like growth factor I receptor, platelet-derived growth factor receptor (PDGFR), TrkE, Axl, epidermal growth factor receptor, etc., appear to be the most abundant receptor-type PTKs in the thyroid; many of which (PDGFR, TrkE, Axl, etc.) have never previously been demonstrated to be expressed in the thyroid. The expression of messenger RNAs (mRNAs) for PDGFR, axl, and trkE in normal thyroid cells was confirmed by Northern blot analysis, and interestingly, the expression levels of PDGFR and trkE mRNAs were decreased in all three thyroid carcinoma cell lines examined (FRO, WRO, and NPA), whereas axl mRNA and protein were overexpressed in 2 of 3 thyroid carcinoma cell lines (FRO and WRO) compared with that in normal tissue. The axl gene was, however, neither amplified nor rearranged. The biological activity of the ligand for Axl, the product of growth arrest-specific gene 6 (Gas6), was then evaluated, demonstrating modest mitogenic activity in thyroid carcinoma cells overexpressing Axl. Furthermore, gas6 mRNA was expressed in FRO cells.Thus, we here identify a variety of PTKs expressed in the thyroid gland, many of which may participate in the regulation of thyroid cell function. Variable expression levels of some PTKs in normal and cancerous cells suggest that there may be an imbalance and disarray of phosphorylation events in thyroid carcinoma cells. Furthermore, Gas6 is identified as a novel growth factor for thyroid carcinoma cells overexpressing Axl receptor tyrosine kinase. (Endocrinology 139: 852-858, 1998) P ROTEIN tyrosine kinases (PTKs) are believed to play a pivotal role in regulating the growth and differentiated functions of eukaryotic cells as components of signal transduction pathways (1). The PTK family is classified into receptor type and nonreceptor type (cytoplasmic type), and includes cellular receptors for certain growth factors and protooncogenes (2).In thyroid cells, activation of PTK cascades, for example, by epidermal growth factor (EGF) and fibroblast growth factor (FGF) are closely linked to cell proliferation and dedifferentiation (3). On the other hand, TSH, a pituitary glycoprotein hormone that is indispensable for stimulating both thyroid cell proliferation and differentiation and largely functions through the cAMP-protein kinase A (serine/threonine kinase)-dependent signal transduction cascade and, to a lesser extent, the C...

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