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The cyclic peptide cyclo(Val-Leu-Leu-D-Phe-Pro)2 (peptide 1) was specifically designed for structural chemistry investigations, drawing inspiration from Gramicidin S (GS). Previous studies have shown that Pro residues within 1 adopt a down-puckering conformation of the pyrrolidine ring. By incorporating fluoride-Pro with 4-trans/cis-isomers into 1, an up-puckering conformation was successfully induced. In the current investigation, introducing hydroxyprolines with 4-trans/cis-isomer configurations (tHyp/cHyp) into 1 gave cyclo(Val-Leu-Leu-D-Phe-tHyp)2 methanol disolvate monohydrate, C62H94N10O12·2CH4O·H2O (4), and cyclo(Val-Leu-Leu-D-Phe-cHyp)2 monohydrate, C62H94N10O12·H2O (5), respectively. However, the puckering of 4 and 5 remained in the down conformation, regardless of the geometric position of the hydroxyl group. Although the backbone structure of 4 with trans-substitution was asymmetric, the asymmetric backbone of 5 with cis-substitution was unexpected. It is speculated that the anticipated influence of stress from the geometric positioning, which was expected to affect the puckering, may have been mitigated by interactions between the hydroxyl groups of hydroxyproline, the solvent molecules, and peptides. [ABSTRACT FROM AUTHOR]

Introduction: Contact hypersensitivity (CHS), a type of delayed‐type hypersensitivity, is induced by hapten exposure to the skin and mucosa. We previously reported that, in a murine model of CHS, the vaginal mucosa (VM) sensitization showed lower T‐cell responses as compared with the abdominal skin sensitization. To investigate mechanisms of impaired CHS by the VM sensitization, we compared migration of hapten‐captured dendritic cells (DCs) in the draining lymph nodes (dLNs) and recruitment of DCs at the sensitized local sites. Methods: Fluorescein isothiocyanate (FITC) or 2,4‑dinitrofluorobenzene (DNFB) was used as hapten, and migration of FITC+ DCs in the dLNs and local recruitment of MHC class II+ and CD11c+ cells were compared between abdominal skin and VM sensitization by flow cytometric analyses and immunohistochemistry. Expression of tumor growth factor (TGF)‐β at mRNA and protein levels, and local recruitment of CD206+ cells were examined after VM sensitization. Results: VM sensitization showed less numbers of FITC+MHC class IIhighCD11c+ migratory DCs in the dLNs at 6 and 24 h, as compared with skin sensitization. Both skin and VM sensitization induced the recruitment of dermal/submucosal DCs at 6 h, but the number of submucosal DCs in the VM was significantly decreased at 24 h. VM showed persistently higher mRNA levels of TGF‐β2/β3 expression than those of the skin before and after sensitization. In the VM sensitization, increment of CD206+MHC class II+ cells was observed especially at the deep lamina propria at 24 h. Most of CD206+ cells were also positive for the binding to Fc chimeric TGF‐β receptor that interacts with all TGF‐β isoforms, suggesting TGF‐β expression. Conclusion: DC migration to dLNs and localization of DCs at the sensitized sites are limited in the VM sensitization. Our results suggest that the existence of TGF‐β‐expressing CD206+ cells may contribute less sensitization ability and CHS responses in the VM. [ABSTRACT FROM AUTHOR]

Some patients with developmental and epileptic encephalopathy (DEE) respond to adrenocorticotropic hormone (ACTH) therapy but relapse soon after. While long‐term ACTH therapy (LT‐ACTH) has been attempted for these patients, no previous studies have carefully assessed adrenal function during LT‐ACTH. We evaluated the effectiveness of LT‐ACTH, as well as adverse effects (AE), including their adrenal function in three DEE patients. Patients underwent a corticotropin‐releasing hormone (CRH) stimulation test during LT‐ACTH, and those with peak serum cortisol below 15 μg/dL were considered to be at high risk of adrenal insufficiency (AI). Two of three responded, and their life‐threatening seizures with postgeneralized electroencephalogram (EEG) suppression decreased. Although no individuals had serious AE, CRH stimulation test revealed relatively weak responses, without reaching normal cortisol peak level (18 μg/dL). Hydrocortisone replacement during stress was prepared in a case with lower cortisol peak than our cutoff level. LT‐ACTH could be a promising treatment option for cases of DEE that relapse soon after effective ACTH treatment. The longer duration and larger cumulative dosage in LT‐ACTH than in conventional ACTH could increase the relative risk of AI. Careful evaluation with pediatric endocrinologists, including hormonal stimulation tests, might be useful for continuing this treatment safely. [ABSTRACT FROM AUTHOR]

Spina bifida (SB) is a congenital neural tube defect that often presents with neurological disability and decubitus ulcers. A 66-year-old woman with SB presented to our hospital with decubitus ulcers and was treated by a plastic surgeon. She was referred to our department because of a mass measuring 5 × 4 cm in the superolateral quadrant of the right breast. The size of the right axillary lymph node (LN) was 2 × 1 cm. A core-needle biopsy revealed an invasive ductal carcinoma. Total mastectomy and axillary LN dissection were planned. However, 2 days prior to surgery, the size of the mass and the LN rapidly increased to 7 × 4 cm and 3 × 2 cm, respectively. Furthermore, the enlarged LN was close to the thoracodorsal artery. Since complete resection was difficult, neoadjuvant chemotherapy was also administered. On day 11 of neoadjuvant chemotherapy, the patient was febrile and developed a decubitus ulcer infection at the buttock. The neutrophil count was within normal limits; thus, she was not diagnosed with febrile neutropenia. Follow-up computed tomography revealed a shrinking of the mass to 5 × 4 cm after the first cycle of neoadjuvant chemotherapy. After 17 days of antibiotic therapy and drainage, total mastectomy and axillary LN dissection were performed. Due to the risk of recurrence of infection, adjuvant chemotherapy was discontinued and hormone therapy was initiated. In conclusion, indications for chemotherapy should be carefully evaluated in SB patients with lower limb paralysis and decubitus ulcers. [ABSTRACT FROM AUTHOR]

Introduction: Mechanisms underlying skin sensitization in allergic contact dermatitis have been actively studied using the murine contact hypersensitivity (CHS) model. However, much less is known about sensitization at the vaginal mucosa (VM). Methods: We developed a CHS model with VM sensitization and epicutaneous elicitation at the ear. We then examined the proliferation activity of lymphocytes, the frequencies of T cells and the differentiation of hapten‐specific T cells in draining lymph nodes (dLNs) after sensitization. Results: Hapten‐specific CHS responses to 2,4‐dinitrofluorobenzene (DNFB), 2,4,6‐trinitrochrolobenzene, and oxazolone assessed by ear swelling suggested that the VM would be an inductive site of CHS to haptens. In the comparisons of CHS responses to each of the three haptens examined, the lower responses in VM‐sensitized mice were observed than skin‐sensitized mice (e.g., DNFB‐induced responses, −56%; p <.001, at 48 h after challenge). Consistent with the CHS responses, the DNFB‐induced proliferation of cells in dLNs examined by 5‐bromo‐2ʹ‐deoxyuridine assay was lower (−62%; p <.001) in VM‐sensitized mice than skin‐sensitized mice. On the other hand, between skin and VM sensitization, no significant differences were observed in the frequencies of interferon‐γ‐producing CD4+ and CD8+ effector, and regulatory T cells in dLNs after sensitization. We also observed no significant differences with respect to differentiation of hapten‐specific T cells based on the examination of cytokine production from dLN cells stimulated in vitro with 2,4‐dinitrobenzene sulfonate. Conclusion: These findings suggested that the lower T cell proliferation after VM sensitization is important for the lower CHS responses with VM sensitization than skin sensitization. [ABSTRACT FROM AUTHOR]

Pheromones are crucial for eliciting social and sexual behaviors in diverse animal species. The vomeronasal receptor type-1 (V1R) genes, encoding members of a pheromone receptor family, are highly variable in number and repertoire among mammals due to extensive gene gain and loss. Here, we report a novel pheromone receptor gene belonging to the V1R family, named ancient V1R (ancV1R), which is shared among most Osteichthyes (bony vertebrates) from the basal lineage of ray-finned fishes to mammals. Phylogenetic and syntenic analyses of ancV1R using 115 vertebrate genomes revealed that it represents an orthologous gene conserved for >400 My of vertebrate evolution. Interestingly, the loss of ancV1R in some tetrapods is coincident with the degeneration of the vomeronasal organ in higher primates, cetaceans, and some reptiles including birds and crocodilians. In addition, ancV1R is expressed in most mature vomeronasal sensory neurons in contrast with canonical V1R s, which are sparsely expressed in a manner that is consistent with the "one neuron–one receptor" rule. Our results imply that a previously undescribed V1R gene inherited from an ancient Silurian ancestor may have played an important functional role in the evolution of vertebrate vomeronasal organ. [ABSTRACT FROM AUTHOR]

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Copyright of Rigakuryoho Kagaku is the property of International Press Editing Center Incorporation and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

[Purpose] The purpose of this study was to clarify the factors affecting longitudinal changes in Activities of Daily Living (ADL) of home-bound elderly disabled, Quality of Life (QOL) and burden of the family caregivers. [Subjects] Data were collected from 11 home-bound elderly disabled receiving rehabilitation services at a day-care center (mean age of 73.7±13.0) and their 11 family caregivers (mean age of 62.7±7.0) who were living at home in Kobe city, Hyogo. [Methods] Capacity to perform ADL was assessed using the Functional Independence Measure (FIM) for the home-bound elderly disabled. The health status, QOL and burden of the family caregivers were also evaluated. [Results] It was revealed that the factors affecting the burden of the family caregivers were related to dementia of the home-bound elderly disabled and QOL of the family caregivers. ADL of the home-bound elderly disabled were related to dementia and the burden of the family caregivers. [Conclusion] These results suggest that in order to reduce the burden of family caregivers, it is important to preserve and improve ADL of the home-bound elderly disabled, and to prevent dementia decline. [ABSTRACT FROM AUTHOR]