There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

Microwave assisted organic synthesis-a review

Background A phase 3 trial was conducted to evaluate the efficacy of a prophylactic quadrivalent vaccine in preventing anogenital diseases associated with human papillomavirus (HPV) types 6, 11, 16, and 18. Methods In this randomized, placebo-controlled, double-blind trial involving 5455 women between the ages of 16 and 24 years, we assigned 2723 women to receive vaccine and 2732 to receive placebo at day 1, month 2, and month 6. The coprimary composite end points were the incidence of genital warts, vulvar or vaginal intraepithelial neoplasia, or cancer and the incidence of cervical intraepithelial neoplasia, adenocarcinoma in situ, or cancer associated with HPV type 6, 11, 16, or 18. Data for the primary analysis were collected for a per-protocol susceptible population of women who had no virologic evidence of HPV type 6, 11, 16, or 18 through 1 month after administration of the third dose. Results The women were followed for an average of 3 years after administration of the first dose. In the per-proto...

/pdf/quadrivalent-vaccine-against-human-papillomavirus-to-prevent-36rchbohnq.pdf

Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases.

Cutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory control by multiple agents interacting via pathways activated by receptor-dependent and -independent mechanisms, in hormonal, auto-, para-, or intracrine fashion. Because of the multidirectional nature and heterogeneous character of the melanogenesis modifying agents, its controlling factors are not organized into simple linear sequences, but they interphase instead in a multidimensional network, with extensive functional overlapping with connections arranged both in series and in parallel. The most important positive regulator of melanogenesis is the MC1 receptor with its ligands melanocortins and ACTH, whereas among the negative regulators agouti protein stands out, determining intensity of melanogenesis and also the type of melanin synthesized. Within the context of the skin as a stress organ, melanogenic activity serves as a unique molecular sensor and transducer of noxious signals and as regulator of local homeostasis. In keeping with these multiple roles, melanogenesis is controlled by a highly structured system, active since early embryogenesis and capable of superselective functional regulation that may reach down to the cellular level represented by single melanocytes. Indeed, the significance of melanogenesis extends beyond the mere assignment of a color trait.

https://www.physiology.org/doi/pdf/10.1152/physrev.00044.2003

Melanin Pigmentation in Mammalian Skin and Its Hormonal Regulation

Background  Vitiligo is a depigmenting disease of the skin, which may derive from programmed melanocyte death or destruction due to inherent sensitivity to oxidative stress arising from either toxic intermediates of melanin, a melanocyte-specific protein, or other sources Tyrosinase-related protein (TRP) -1 has been shown to be involved not only in melanin biosynthesis but also in the prevention of premature melanocyte death in animals



Objectives  To clarify the biological role of human TRP-1 in melanocyte survival



Methods  Cultured melanocyte strains from an active advancing border of vitiligo were established and studied



Results  The established ‘vitiligo melanocytes’ showed large perikaryon and stubby dendrites They showed early cell death when exposed to oxidative stress (ultraviolet B) and increased and abnormal immunostaining and immunoprecipitation by antibodies against human and mouse TRP-1, indicating an altered synthesis and processing of TRP-1 In pulse–chase and sequential immunoprecipitation experiments, vitiligo melanocytes revealed abnormal protein–protein interaction with calnexin, a melanogenesis-associated chaperone, suggesting altered folding and maturation of nascent TRP-1 polypeptides Northern blot analysis indicated a decreased expression of TRP-1 mRNA, but heteroduplex analysis and verification of the mutation at the carboxy terminus of TRP-1 by restriction enzyme analysis did not show any abnormality



Conclusions  Our study suggests that the early cell death of vitiligo melanocytes is related to their increased sensitivity to oxidative stress, which may arise from complex processes of abnormal synthesis and processing of TRP-1 and its interaction with calnexin

Increased sensitivity of melanocytes to oxidative stress and abnormal expression of tyrosinase-related protein in vitiligo.

We showed previously that herpes simplex virus type 1 (HSV-1) suppresses the interferon (IFN) signaling pathway during the early infection stage in the human amnion cell line FL. HSV-1 inhibits the IFN-induced phosphorylation of Janus kinases (JAK) in infected FL cells. In the present study, we showed that the suppressor of cytokine signaling-3 (SOCS3), a host negative regulator of the JAK/STAT pathway, is rapidly induced in FL cells after HSV-1 infection. Maximal levels of SOCS3 protein were detected at around 1 to 2 h after infection. This is consistent with the occurrence of HSV-1-mediated inhibition of IFN-induced JAK phosphorylation. The HSV-1 wild-type strain VR3 induced SOCS3 more efficiently than did mutants that are defective in UL41 or UL13 and that are hyperresponsive to IFN. Induction of the IRF-7 protein and transcriptional activation of IFN-α4, which occur in a JAK/STAT pathway-dependent manner, were poorly induced by VR3 but efficiently induced by the mutant viruses. In contrast, phosphorylation of IRF-3 and transcriptional activation of IFN-β, which are JAK/STAT pathway-independent process, were equally well induced by the wild-type strain and the mutants. In conclusion, the SOCS3 protein appears to be mainly responsible for the suppression of IFN signaling and IFN production that occurs during HSV-1 infection.

Induction of Suppressor of Cytokine Signaling-3 by Herpes Simplex Virus Type 1 Contributes to Inhibition of the Interferon Signaling Pathway

Quantitative Analysis of Eumelanin and Pheomelanin in Hair and Melanomas

Assembly, target-signaling and transport of tyrosinase gene family proteins at the initial stage of melanosome biogenesis are reviewed based on our own discoveries Melanosome biogenesis involves four stages of maturation with distinct morphological and biochemical characteristics that reflect distinct processes of the biosynthesis of structural and enzymatic proteins, subsequent structural organization and melanin deposition occurring in these particular cellular compartments The melanosomes share many common biological properties with the lysosomes The stage I melanosomes appear to be linked to the late endosomes Most of melanosomal proteins are glycoproteins that should be folded or assembled correctly in the ER through interaction with calnexin, a chaperone associated with melanogenesis These melanosomal glycoproteins are then accumulated in the trans Golgi network (TGN) and transported to the melanosomal compartment During the formation of transport vesicles, coat proteins assemble on the cytoplasmic face of TGN to select their cargos by interacting directly or indirectly with melanosomal glycoproteins to be transported Adapter protein-3 (AP-3) is important for intracellular transport of tyrosinase gene family proteins from TGN to melanosomes Tyrosinase gene family proteins possess a di-leucine motif in their cytoplasmic tail, to which AP-3 appears to bind Thus, the initial cascade of melanosome biogenesis is regulated by several factors including: 1) glycosylation of tyrosinase gene family proteins and their correct folding and assembly within ER and Golgi, and 2) supply of specific signals necessary for intracellular transport of these glycoproteins by vesicles from Golgi to melanosomes

Assembly, target-signaling and intracellular transport of tyrosinase gene family proteins in the initial stage of melanosome biogenesis.

In order to identify a means to reduce scar formation of the skin after incision, this study examined the effect of local administration of basic fibroblast growth factor (bFGF) in humans. bFGF was administered to a sutured wound immediately after an operation. The drug was injected once into the dermis of the margins of wounds using a 27G needle or rinsing after performing dermostitches. The lengths of the treated wounds varied from 1 to 32 cm, and the subjects were 2-86 years old. Sutured wounds after excision of skin tumors from the face, trunk, and limbs and sutured wounds such as those at the donor sites of full-thickness skin grafts were treated with low-dose bFGF injections (0.1 microg/cm wound; Group 2), high-dose bFGF injections (1 microg/cm wound; Group 3), and rinsed with high-dose bFGF (1 microg/cm wound; Group 4). No patient treated with bFGF had hypertrophic scars, while some patients had hypertrophic or very wide scars in the control group (Group 1), and the ratios of minimum scarring of Group 2 (p<0.001), Group 3 (p<0.0001), and Group 4 (p<0.0001) were statistically significantly higher than those of Group 1. Postoperative administration of bFGF inhibited hypertrophic scarring and widening of remaining scars without any serious side effects.

Kowichi Jimbow

Papers

Increased sensitivity of melanocytes to oxidative stress and abnormal expression of tyrosinase-related protein in vitiligo.

Induction of Suppressor of Cytokine Signaling-3 by Herpes Simplex Virus Type 1 Contributes to Inhibition of the Interferon Signaling Pathway

Quantitative Analysis of Eumelanin and Pheomelanin in Hair and Melanomas

Assembly, target-signaling and intracellular transport of tyrosinase gene family proteins in the initial stage of melanosome biogenesis.

Basic fibroblast growth factor reduces scar formation in acute incisional wounds