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Notes: Coherent infrared (IR) image bundle was developed for the delivery of the IR thermal image. The fiber employed was the As2S3 glass core of 65 μm diam and Teflon (perfluoronated ethylene propylene) cladding of 75 μm diam, which has the transmission range in the wavelength region between 1 and 7 μm. Two kinds of bundles of 100 cm long were prepared, which consisted of 1550 fibers (NPB75-1550) and of 8400 fibers (NPB75-8400). The IR imaging system was constructed by coupling the bundle to an IR television camera. The performance of the system was investigated by detecting the thermal image of an operating LSI package.

Notes: In order to identify a means to reduce the scar formation of the skin after incision, this study examined the wound healing effect of bFGF in humans. BFGF was administered at dose of 0.1 and 1 μg per cm of sutured immediately after an operation. The drug was injected once into the dermis of the margins of wounds using a 27 G needle attached to a 1-ml syringe to the patients. The lengths of the treated wounds varied from 1.5 cm to 23 cm, and the subjects were 2 to 76 years old. Sutured wounds after excision of skin tumors from the face, trunk and limbs and the sutured wounds such as those at the donor sites of full thickness skin grafts were treated with low dose bFGF injections. Postoperative administration of bFGF, inhibited scaring and accelerated healing without any serious side effects. Although double–blind studies are needed, we expect that so-called scar-less surgery may be possible by establishing of more sophisticated methods for administering bFGF and its combination with other drugs and/or gene therapy in the future.

Notes: Apoptosis has been shown to play an important role in the regulation of wound healing, and growth factors can mediate this process. In this study, we examined the relationship between the degree of healing and the level of apoptosis in full-thickness-incisional skin wounds, which were treated by conventional suturing with or without intradermal injection of bFGF (0.1 μg and 1 μg/cm of wound). The width of wound tissue showed that the degree of granulation formation in the 1 μg-bFGF-treated group significantly increased on day 7, whereas the degree of scar formation significantly decreased on days 14 and 28. Similarly, apoptotic cells significantly increased in the number on day 4 in the 1 μg-bFGF-treated group compared with that of the control group (p = 0.024), and decreased on days 14 and 28. These findings therefore, suggest that the accelerated apoptosis in the bFGF-treated wounds contributes to the decreased cellularity in inflammatory change through elimination of cells with apoptosis, which resulted also in the reduction of scar formation. It therefore hypothesized that apoptosis is involved in the maturation of an acute wound into scar formation, and that bFGF can accelerate this process.

Notes: Hepatocyte growth factor (HGF) is a ligand for the c-Met receptor tyrosine kinase. This study was aimed to characterize the role of the HGF gene combined with basic fibroblast growth factor (bFGF) protein in wound healing by administering both of them locally to acute incisional skin wounds created on the backs of rats. The bFGF protein and the HGF gene were administered intradermally after incisional surgery. Apoptotic cells in wound lesions were identified by the terminal deoxynucleotide transferase-mediated nick-end labeling method, as well as by immunological detection of active caspase-3. While there was almost complete suppression of apoptosis with well-organized wound healing in animals treated with the HGF gene, the combination of bFGF protein and the HGF gene paradoxically resulted in less scarring along with the promotion of apoptosis. Histopathological examination revealed that scar formation was least apparent in rats treated with both bFGF and the HGF gene compared with controls or those treated with the bFGF or the HGF gene alone. It is thought that the combined administration of bFGF and the HGF gene immediately after skin incision may make the healing process occur closer to tissue regeneration through the induction of apoptosis, which occurred 1 week after surgery. HGF supplementation through gene therapy combined with bFGF protein may be an effective strategy for treating wounds, as it increases the apparent regeneration of the dermis to allow for “scarless wound healing.”

Notes: A 58-year-old Japanese man visited our clinic in December 2000 with a complaint of an erythematous plaque with reddish papules and pigmentation on the penis shaft and glans. He noticed the lesion 1 month before his visit. He denied any previous homosexual activity. His wife denied any genital skin lesion or gynecologic abnormality. No history of human immunodeficiency virus infection could be obtained.Physical examination of the skin lesion revealed an asymptomatic, flat-topped, approximately 10-mm-sized, reddish-brown keratotic plaque on the penis shaft. It showed an irregular surface, irregular border, and color variegation. Multiple, small, reddish-brown papules and plaques were distributed on the surrounding penis shaft and glans (〈link href="#f1"〉Fig. 1). The patient had no symptomatic signs. No lymphadenopathy was noted in the inguinal area.〈figure xml:id="f1"〉Figure 1 〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD1307_1:IJD_1307_f1"/〉Clinical features of BP lesions on the penis. A keratotic plaque shows an irregular surface, irregular border, and color variegation, and is surrounded by small, reddish-brown papulesA biopsy specimen revealed parakeratosis and an irregularly acanthotic epidermis composed of abnormal keratinocytes exhibiting cellular atypia and mitotic figures. The tumor cells had large, hyperchromatic, and pleomorphic nuclei (〈link href="#f2"〉Fig. 2). These lesions were diagnosed as bowenoid papulosis (BP). For treatment, an operative excision with a 3 mm margin was performed.〈figure xml:id="f2"〉2〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD1307_1:IJD_1307_f2"/〉Histologic features of the BP lesion. A parakeratotic and irregularly acanthotic epidermis is composed of abnormal keratinocytes exhibiting cellular atypia and mitotic figures. The tumor cells have large, hyperchromatic, and pleomorphic nucleiDNA was extracted from blocks of BP and non-BP, normal-looking skin tissue. Polymerase chain reaction (PCR) was performed utilizing L1 consensus primer set MY09 and MY11 (Bernard HU, Chan SY, Manos MM, et al. Identification and assessment of known and novel human papillomaviruses by polymerase chain reaction amplification, restriction fragment length polymorphisms, nucleotide sequence, and phylogenetic algorithms. J Infect Dis 1994; 170: 1077–1085). MY09/11 consensus PCR generated an approximately 450-base-pair fragment from all of the samples (〈link href="#f3"〉Fig. 3). Nucleotide sequencing revealed that the amplified L1 sequences were identical to that of human papillomavirus (HPV) type 16 (nucleotide positions 6582–7018). All of the L1 sequences from the BP lesion and the normal regions were identical. Our case contained the prototype sequence reported by Dürst et al. (Dürst M, Gissmann L, Ikenberg H, zur Hausen H. A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proc Natl Acad Sci USA 1983; 80: 3812–3815).〈figure xml:id="f3"〉3〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD1307_1:IJD_1307_f3"/〉Amplification of the L1 sequence from a BP lesion and surrounding tissues. The polymerase chain reaction was carried out using MY09 and MY11 consensus primers. Lanes from left to right: M, 1-kilobase ladder marker; N, negative control (H2O); P, positive control (HPV16 DNA); 1, DNA from BP lesion; 2 and 3, DNA from surrounding tissues consisting of normal skin. An arrow indicates the 450-base-pair bands

Notes: Abstract Three species of E6/E7 cDNAs of human papillomavirus type 16 (HPV16) for the full-length E6/E7 and spliced E6*I/E7 and E6*II/E7 mRNAs were synthesized by reverse transcriptase-(RT-)PCR from RNA of the cervical carcinoma cell line SiHa. Two cDNA mutants carrying point mutations in either a splice donor site or acceptor site within the E6 open reading frame were also constructed. These HPV16 E6/E7 cDNAs were cloned under the SV40 enhancer/promoter and the MMTV LTR to examine the activities ofras-collaborative transformation and induction of cellular DNA synthesis, both of which depend on the E7 gene product. The E6*II/E7 cDNA and two mutated cDNAs deficient in the spliced mRNA transcription showed lower levels of both activities than the full-length E6/E7 and the E6*I/E7 cDNA. The rat cell lines carrying each of the E6/E7 cDNAs contained the E6/E7 mRNA species expected. A small amount of E6*I/E7-sized mRNA was transcribed from a splice-donor site mutant of the E6/E7 cDNA, which turned out to be a transcript derived from a cryptic splice donor site six bases upstream from the conventional site. Among NIH3T3 cells carrying one of the above-mentioned E6/E7 cDNAs, the cells expressing E6*I/E7 mRNA [cells carrying cF(wt) and c*I] produced an amount of E7 protein comparable with those carrying the E7 or E6E7 region. These results suggest that the E6*I/E7 is the mRNA that is important for the efficient expression of E7 product from the HPV16 E6/E7 region.