Late-phase urticaria Update

In ordinary urticaria, individual lesions disappear within 24 hours. However, we sometimes encounter patients whose eruptions last longer than 24 hours, but without evidence of vasculitis or a history of exposure to pressure. In these patients, histology reveals a perivascular infiltration, predominantly of eosinophils, depending on the timing of the biopsy. Unlike urticarial vasculitis, no immunoglobulins, complement deposition, or endothelial fibrinoid degeneration is observed. The peripheral eosinophil counts and serum complement levels appear within normal range. No protein urea or joint pain is observed, and the lesions can be controlled only by systemic glucocorticoids. We recognize such a urticarial reaction as a different clinical entity than usual urticaria, which is presumably mediated by latephase inflammatory reaction in immediate hypersensitivity.     

Melanotic oncocytic metaplasia of the nasopharynx: a case report with a focus on immunohistochemical analyses and literature review

Melanotic oncocytic metaplasia (MOM) of the nasopharynx is an extremely rare lesion, with only 21 cases reported in English literature to date. MOM typically occurs near the Eustachian tube opening in Asian men in their 60 s to 70 s. Here, we present a case of MOM in a 57-year-old Japanese man who is a heavy smoker. The patient did not have complaints; MOM was diagnosed incidentally as 4 flat elevated lesions with brown to black discoloration, ranging from 2 to 3 mm in maximal diameter, were found in the right torus tubarius. On suspecting melanoma, the largest lesion was biopsied. Microscopic examination identified both oncocytic metaplasia and melanin pigmentation of the epithelium in the same gland. Upon immunohistochemical examination, melanocytes displayed reactivity for 3 out of 4 melanocytic markers; immunopositivity for S-100 protein, Melan-A, and MITF and immunonegativity for HMB-45 was observed. Normal melanocytes in the nearby surface respiratory epithelium displayed the same pattern of immunoreactivity. Immunopositivity for S-100 protein and immunonegativity for HMB-45 have been previously reported in MOM. Reduction of stimulation of melanocytes in a longstanding lesion like MOM may explain the immunonegativity for HMB-45. S-100 protein, in conjunction with more specific marker for melanocytes, Melan-A or MITF, could prove the definite presence of melanocytes in this case of MOM. As it has been shown by previous reports that MOM pursues a benign course, it will be sufficient to follow up the patients regularly for the remaining 3 lesions.     

Homology modeling in drug discovery: Overview,current applications,and future perspectives

Homology modeling is one of the computational structure prediction methods that are used to determine protein 3D structure from its amino acid sequence. It is considered to be the most accurate of the computational structure prediction methods. It consists of multiple steps that are straightforward and easy to apply. There are many tools and servers that are used for homology modeling. There is no single modeling program or server which is superior in every aspect to others. Since the functionality of the model depends on the quality of the generated protein 3D structure, maximizing the quality of homology modeling is crucial. Homology modeling has many applications in the drug discovery process. Since drugs interact with receptors that consist mainly of proteins, protein 3D structure determination, and thus homology modeling is important in drug discovery. Accordingly, there has been the clarification of protein interactions using 3D structures of proteins that are built with homology modeling. This contributes to the identification of novel drug candidates. Homology modeling plays an important role in making drug discovery faster, easier, cheaper, and more practical. As new modeling methods and combinations are introduced, the scope of its applications widens.     

Acute physiological responses to physiotherapy applications pre and post autologous stem cell transplantation: an experimental study

Objective

We aimed to investigate the acute physiological responses (APR) to physiotherapy applications in patients undergoing autologous stem cell transplantation (ASCT), the difference between pre- and post-ASCT according to APR.

Methods

Twenty-six patients who were hospitalized for ASCT attended regular physiotherapy program. APR was recorded in the beginning and at the end of each exercise session. The differences in APR were calculated for each session. The mean values of the differences in APR were computed in pre-conditioning, pre-, and post-ASCT. Daily complete blood counts were also recorded during ASCT.

Results

Hemoglobin and platelet counts were significantly lower pre- and post-ASCT. Neutrophil counts were significantly lower post-ASCT. The difference in systolic blood pressure (SBP) in the beginning and at the end of the exercise sessions was significantly higher post-ASCT in comparison to pre-ASCT.

Conclusion

There was no significant change in APR except the SBP which suggests that similar level of exercise intensity could be tolerated in pre- and post-ASCT periods as well as preconditioning.     

The risk of lymph node metastasis in mucosal gastric carcinoma: especially for a mixture of differentiated and undifferentiated adenocarcinoma

Background/Aims: Endoscopic submucosal dissection (ESD) is gaining wider acceptance for the treatment of early gastric carcinoma (EGC) and its indication has been extended to mucosal gastric carcinoma with undifferentiated component in some institutes. Our aims were to confirm the frequency of lymph node metastasis in such cases and clarify the demarcation in indications for ESD. Methodology: We evaluated medical data of 287 patients with mucosal gastric carcinoma who underwent surgical resection between 1996 and 2008. The tumours were histologically classified into purely differentiated (PD), differentiatedpredominant mixed (DPM), undifferentiated-predominant mixed (UPM) and purely undifferentiated (PU) types. Results: Lymph node metastasis was identified in seven (2.4%) of the 287 patients and was detected more frequently in UPM (10%, two of 20) and PU (4%, four of 98), compared with PD (none of 148) (p=0.01 and 0.02, respectively). In mixed-type carcinoma, size was a significant risk factor for lymph node metastasis (p=0.04). Conclusions: It might be better to select gastrectomy rather than ESD for the treatment of mucosal gastric carcinoma with an undifferentiated component.     

Life-Time Adversities,Reported Thirteen Years After a Suicide Attempt: Relationship to Recovery, 5HTTLPR Genotype,and Past and Present Morbidity

In this study, we investigated how adversities related to past and present morbidity, and genotype. Forty-two, suicide attempters and 22 matched control patients were followed-up after 13 years. Life-time adversities were explored in an interview, and the patients were reassessed psychiatrically. The serotonin-transporter-linked promotor region (5-HTTLPR) was typed. More adversities were reported by suicide attempters than controls, and by still-ill than recovered suicide attempters. Adversities reported at follow-up were related to psychiatric morbidity at follow-up, but not to morbidity 13 years earlier. The 5-HTTLPR, genotype was associated with reported adversities, but not chances of recovery. Adversities potentially affected chronic morbidity. 5-HTTLPR genotype did not affect long-term recovery.     

Quality-Control Culture System Restores Diabetic Endothelial Progenitor Cell Vasculogenesis and Accelerates Wound Closure

Delayed diabetic wound healing is, in part, the result of inadequate endothelial progenitor cell (EPC) proliferation, mobilization, and trafficking. Recently, we developed a serum-free functional culture system called the quality and quantity culture (QQc) system that enhances the number and vasculogenic potential of EPCs. We hypothesize that QQc restoration of diabetic EPC function will improve wound closure. To test this hypothesis, we measured diabetic c-kit⁺Sca-1⁺lin⁻ (KSL) cell activity in vitro as well as the effect of KSL cell–adoptive transfer on the rate of euglycemic wound closure before and after QQc. KSL cells were magnetically sorted from control and streptozotocin-induced type I diabetic C57BL6J bone marrow. Freshly isolated control and diabetic KSL cells were cultured in QQc for 7 days and pre-QQc and post-QQc KSL function testing. The number of KSL cells significantly increased after QQc for both diabetic subjects and controls, and diabetic KSL increased vasculogenic potential above the fresh control KSL level. Similarly, fresh diabetic cells form fewer tubules, but QQc increases diabetic tubule formation to levels greater than that of fresh control cells (P < 0.05). Adoptive transfer of post-QQc diabetic KSL cells significantly enhances wound closure compared with fresh diabetic KSL cells and equaled wound closure of post-QQc control KSL cells. Post-QQc diabetic KSL enhancement of wound closure is mediated, in part, via a vasculogenic mechanism. This study demonstrates that QQc can reverse diabetic EPC dysfunction and achieve control levels of EPC function. Finally, post-QQc diabetic EPC therapy effectively improved euglycemic wound closure and may improve diabetic wound healing.Although blood supply is essential for tissue viability, new blood vessel formation is critical for tissue recovery, regeneration, and repair. Postnatal new blood vessel formation was long thought to be restricted to angiogenesis, the sprouting of new blood vessels from existing vascular structures. However, in 1997, we demonstrated that the de novo formation of new blood vessel derived from bone marrow (BM)-derived cells (i.e., vasculogenesis) is an important part of postnatal healing (1–3). The BM-derived endothelial progenitor cells (EPCs) are precursors of endothelial cells (ECs) and are characterized by their surface expression of KDR, CD133, and CD34 for humans and of lineage-negative c-kit⁺Sca-1⁺ (KSL) cells for murine BM cells (4–6).After injury, locally derived circulating factors mobilize EPCs from their endosteal BM niche. Circulating BM-derived EPCs traffic to the site of injury, experience diapedesis, cluster, tubulize, and canalize to form nascent vessels that inosculate with the existing vasculature (7,8). EPCs have been shown to revascularize numerous ischemic tissues, including myocardium (i.e., myocardial infarction), brain (i.e., cerebral infarction), and skin (i.e., cutaneous wounding) (9,10). Whereas BM-derived EPCs contribute to only 25% of newly formed endothelium in healing tissues, when EPC function is impaired there are marked deficits in tissue repair mechanisms (11,12).Compared with nondiabetic patients, diabetic EPCs have impaired proliferation, adhesion, migration, and differentiation (13–15). Although the pathogenesis of impaired diabetic wound healing is multifactorial, EPC dysfunction plays a central role (16,17). These intrinsic diabetic EPC vasculogenic impairments may result in >83,000 amputations each year and a postamputation 3-year mortality rate of 75.9% (18). In preclinical studies, the administration of exogenous EPCs has improved ventricular function after myocardial ischemia (19,20), enhanced neuronal recovery after cerebral vascular occlusion, and accelerated restoration of blood flow to ischemic limbs (13,16,17,21–23). Based on these exciting results, we have conducted a phase 3 clinical trial of autologous granulocyte colony-stimulating factor–mobilized peripheral blood EPC therapy for nonhealing diabetic foot patients (24). The results demonstrated that more successful therapeutic results were seen in patients receiving high-vasculogenic EPCs. From these results, we hypothesize that successful autologous diabetic EPC therapy relies on the vasculogenic function of transplanted EPCs and speculate that the intrinsic diabetic EPC dysfunction will limit the efficacy of the therapeutic strategy (25,26).Recently, our group established a serum-free quality and quantity culture (QQc) system (containing stem cell factor, thrombopoietin, vascular endothelial growth factor, interleukin-6, and Flt-3 ligand) that enhances the vasculogenic potential of EPCs (27). We hypothesize that QQc can reverse the detrimental effects of diabeties-induced EPC dysfunction and can supply a sufficient number of functional EPCs for adoptive autologous cell–based therapy for diabetic patients. In the current study, we tested this hypothesis.     

Role of Neurokinin B and Dynorphin A in pituitary gonadotroph and somatolactotroph cell lines

The role of Neurokinin B (NKB) and Dynorphin A (Dyn) in the regulation of the hypothalamic pituitary axis is an important area of recent investigation. These peptides are critical for the rhythmic release of GnRH, which subsequently stimulates the secretion of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The present study utilized the gonadotroph cell line LβT2 and the somatolactotroph GH3 cell line to examine the possible role of these peptides in pituitary hormone secretion. The NKB receptor (NK3R) and the Dyn receptor (the κ-opiate receptor (KOR)) were both detected in LβT2 cells and GH3 cells. NKB, by itself, failed to increase gonadotropin LHβ and FSHβ promoter activities and did not modulate the effects of GnRH on gonadotropin promoter activity. In GH3 cells, NKB significantly increased TRH-induced PRL promoter activity although NKB alone did not have an effect on basal PRL promoter activity. Dyn had no effect on gonadotropin promoters alone or in combination with GnRH stimulation. PRL promoters stimulated by TRH were not significantly changed by Dyn. TRH-induced PRL promoter activity was further increased in the presence of higher concentrations of NKB, whereas Dyn did not have a significant effect on the PRL promoter even at a high concentration. In addition, TRH-induced ERK (Extracelluar signal-regulated kinase) activation was enhanced in the presence of NKB. Our current study demonstrated that NKB had a stimulatory effect on PRL expression in a PRL-producing cell, but had no effect on gonadotropin secretion from a gonadotroph cell line.     

Icteric acute hepatitis E with no response of immunoglobulin M class anti‐hepatitis E virus antibody

A 68‐year‐old Japanese man developed icteric acute hepatitis during periodic care after undergoing gastrectomy due to early gastric cancer. The routine serological markers for hepatitis A, B and C viruses were all negative. Although the liver enzymes spontaneously recovered without any specific therapy, cholestasis was relatively prolonged and successfully treated with prednisolone. Determination of serum hepatitis E virus (HEV) RNA revealed the transient infection of HEV, and both immunoglobulin (Ig)A and IgG class anti‐HEV antibodies were detected after the disease onset, whereas those were negative when measured 3 weeks prior to the onset. In addition, the titer of serum IgA class antibody was associated with the clinical signs of hepatitis. In contrast, no IgM class antibody was detected throughout the course. This case suggests that screening only with IgM class antibody is not sufficient to detect acute HEV infection.