Somatic gene therapy is a potentially useful strategy for the delivery of growth factors or cytokines to enhance wound healing. Experimental excisional and incisional wounds in impaired-healing diabetic mice (db/db) were treated with aFGF and with a plasmid coding for aFGF. A eukaryotic expression plasmid composed of the Hst signal peptide sequence in-frame with the human aFGF sequence was used. Transfection of tissues was accomplished either by direct plasmid uptake or by uptake facilitated with cationic liposomes. The results show that the closure of excisional wounds was significantly accelerated (p < 0.05) by topical application of human recombinant aFGF or by transfection with the aFGF plasmid but not by vehicle or control plasmid not containing the aFGF sequence. In incisional wounds, aFGF or transfection with the plasmid significantly increased the wound-breaking strength compared to their corresponding controls (p < 0.05). Quantitative histology of the plasmid-treated incisional wound sections revealed improved wound quality. The transcription of mRNA from human aFGF cDNA in the incisional wound tissue extracts was confirmed by RT-PCR, and the expressed aFGF was detected by immune dot blot and immunohistochemistry assays. The transfection was a transient process with a peak at 9 d in db/+ (littermates of the diabetic mice) incisional wounds, at 36 d in db/db incisional wounds, and at 27 d in db/db excisional wounds. Cells transfected with human aFGF occupied up to 6.4% of the transectional area in the wound sites. Thus, aFGF gene delivery resulted in both gene expression and a functional improvement in healing.

This study provides evidence that supplemental bFGF can increase vascularity to skin flaps in previously irradiated porcine skin tissue. Histologically, radiation did not prevent the angiogenic effect of bFGF.

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Clear cell morphology in primary thyroid neoplasms has been reported in follicular carcinomas, follicular adenomas, oncocytic/Hürthle cell carcinomas, papillary carcinomas, poorly differentiated/insular carcinomas, and medullary carcinomas.1-5 Such cases are rarely encountered and when reported are more numerous in the histopathology literature than in writings pertaining to cytology. In some instances, clear cell morphology in primary thyroid neoplasms has been attributed to cytoplasmic glycogen accumulation and in other examples to the presence of cytoplasmic lipid material. Of note, rare examples of signet ring cell morphology have also been reported in thyroid tumors, and some authors have attributed clear cell changes in oncocytic thyroid cells to cystic dilation of cytoplasmic mitochondria. 6The photomicrographs in the current report are derived from fine needle aspiration smears and subsequent histopathologic sections from a thyroid lobectomy specimen that housed a 7 cm, partially-encapsulated thyroid mass in a 70-year-old male patient. Both the cytology and the histology slides show epithelial cells with prominent clear cell cytoplasmic change. Clear cell cytoplasmic features were focused in the Diff-Quik stained FNA slides (Fig. C-1a) and were most evident at the edges of cell groups. Papanicolaou stained FNA smears (Fig. C-1b) were highly cellular and showed three-dimensional (3D) aggregates of monotonous and crowded classical oncocytes with moderately abundant granular eosinophilic cytoplasm and with cytoarchitectural microfollicles. In hematoxylin and eosin stained sections made from the mass in the subsequent lobectomy specimen (Fig. C-1c), both classical oncocytic and clear cell fields are seen. Of note, the nuclei of both cell types are strikingly similar, with open chromatin, rounded nuclear contours, and slightly eccentric prominent nucleoli. Areas not photographed showed both vascular and capsular permeation, qualifying the resected tumor as a carcinoma.Positive ancillary thyroid transcription factor 1 (TTF-1) immunohistochemistry testing (Fig. C-1d) helped to confirm the thyroid epithelial derivation of both cell types and helped to exclude that the clear cell differentiation did not represent foamy macrophages or metastatic clear cell carcinoma from some other body site. The presence of the TTF-1 immunoreactivity was discussed in the diagnostic surgical pathology report and was felt relevant to be reported as clear cell tumors are more commonly encountered in other body sites such as the kidneys. TTF-1, a homeobox protein, which in humans is encoded by the NKX2-1 gene, is known as a thyroid specific enhancer binding protein, and it regulates transcription of proteins specific for the thyroid, lungs, and diencephalon. In some instances, renal cell carcinomas can present with metastasis to distant body sites or can metastasize to richly vascular organs such as the thyroid after long disease free intervals. In such cases, the differential diagnosis of metastatic renal cell carcinoma may not be cl...