T cell response of I-Aq mice to self type II collagen: meshing of the binding motif of the I-Aq molecule with repetitive sequences results in autoreactivity to multiple epitopes

Type II collagen (CII) is of immunological interest because of its repetitive structure and properties as an autoantigen. The mouse gene has recently been cloned, thus enabling T cell-defined epitopes to be identified. Multiple novel epitopes on mouse CII are here detected in the autoreactive T cell response. The major response is directed to an epitope with residues 707-721 located on the CB10 fragment. Some 25 other epitopes are also recognized, including the autologous homologue of the 256-270 epitope which dominates in the response to foreign collagen. The cells reactive with mouse collagen peptides were of Th1 type, as judged by release of IFN-gamma. No significant reactivity was detected to mouse CII peptides during ongoing disease. Alignment of the mouse epitopes revealed a sequence motif with characteristic side chains at residues P1, P4 and P7, and to a lesser extent at P5, within a nonamer core sequence. Binding of these epitopes was simulated in a computer model of the I-Aq molecule, where peptides with anchor residues at P1, P4 and P7 were indeed found to fit the binding groove best. The spacing of pockets and the fine structure of the binding surface of the I-Aq molecule meshes with the repetitive structure of the collagen (X-Y-Gly), thus providing a likely explanation for the occurrence of multiple epitopes. Comparison with human DR binding motifs showed that the I-Aq motif resembles most closely that of the DR4 subtypes which predispose for rheumatoid arthritis.      

Nasal mucosal expression of nitric oxide synthases in patients with allergic rhinitis and its relation to asthma.

BACKGROUND: Nitric oxide (NO) has contradictory roles in the pathophysiology of allergic inflammation in both allergic rhinitis (AR) and asthma. Small amounts of NO produced by constitutive NO synthase (NOS) is anti-inflammatory, whereas large amounts produced by inducible NOS (iNOS) are proinflammatory. OBJECTIVE: To investigate the difference in constitutive endothelial NOS (eNOS) and iNOS expression in nonallergic and allergic mucosa and the possible relation of this to the coexistence of asthma in seasonal AR. METHODS: Seventeen patients (10 women and 7 men) with seasonal AR and 9 nonallergic patients (5 women and 4 men) with nasal septum deviation were enrolled. Inferior turbinate nasal biopsy specimens were obtained in all. Levels of eNOS and iNOS expressed as immunohistochemical scores (HSCOREs) were determined immunohistochemically from the specimens. RESULTS: The mean +/- SD HSCOREs for eNOS in patients with seasonal AR were not significantly different from those of the nonallergic controls (1.85 +/- 0.78 vs 1.63 +/- 0.54; P = .12). On the other hand, the mean +/- SD HSCOREs for iNOS were significantly higher in patients with seasonal AR (1.75 +/- 0.75 vs 0.71 +/- 0.6; P = .004). Furthermore, although eNOS expression was not different between seasonal AR patients with and without asthma, the mean +/- SD HSCOREs for iNOS were significantly higher in the patients with asthma (1.93 +/- 0.78 vs 1.65 +/- 0.55; P = .01). CONCLUSION: Increased expression of iNOS might have a role in the development of allergic inflammation in upper and lower airways and in comorbidity of AR and asthma.     

The current perspective on genetic and epigenetic factors in sperm maturation in the epididymis

Male infertility affects approximately 30% of infertile couples. As spermatozoa mature in the epididymal lumen, their potential for mobility increases, and their protein, lipid and small RNA (sRNA) content changes, whereas capacitation and fertilisation take place in the female reproductive tract. Both of the latter processes are affected by maturation, because impaired maturation causes premature capacitation and fertilization. The epididymis produces a suitable environment for sperm maturation via ion transport, vesicle secretion and protein matrix formation. The microenvironment for sperm maturation varies in three broad segments: the caput, the corpus and the cauda epididymis. Epididymosomes transfer proteins, lipids and sRNAs from the epididymal epithelium to spermatozoa and genetic alterations of epididymal genes can lead to decreased sperm motility, morphological abnormalities of spermatozoa and subfertility. Genetic factors are involved in all aetiological categories in male infertility. However, studies conducted on the genes involved in epididymal functions are limited. The sRNA content of spermatozoa changes during epididymal migration, and these sRNAs play a role in embryo development and epigenetic inheritance. This review aims to clarify the role of the epididymal epithelium in the maturation of spermatozoa in light of the current molecular genomic knowledge.     

Pain during sexual activity and ejaculation following hernia repair: A retrospective comparison of transabdominal preperitoneal versus Lichtenstein repair

Pain during sexual activity and ejaculation are the unspoken long-term complications of groin hernia repair. Laparoscopic surgical techniques are associated with decreased post-operative pain and earlier return to daily activities, but its effect on these complications is unclear. This study aims to investigate the effect of transabdominal preperitoneal repair (TAPP) on de-novo pain during sexual intercourse and ejaculation and to compare with open repair. For this reason, two groups were determined according to the surgical technique: the Lichtenstein repair and the TAPP groups and a questionnaire was sent to the patients a minimum of 6 months following the surgery. A total of 317 patients included, as 115 in TAPP and 202 in Lichtenstein repair group. No significant difference was observed concerning pre-operative pain during sexual activity and ejaculation in both groups (p = .75, p = .56). Following the surgery, the number of patients experiencing painful sexual activity was significantly higher in the Lichtenstein repair group compared to the TAPP group (19.3% vs. 11.3%, respectively, p = .03). The post-operative painful ejaculation rate was also significantly lower for the TAPP group (p = .04). The lower rates of post-operative dysejaculation and pain during sexual activity can be achieved with the advantage of laparoscopic surgery.     

Tuberculosis in renal transplant recipients

BACKGROUND: Tuberculosis is an important cause of morbidity and mortality in renal transplant recipients, but there are insufficient data regarding the efficacy and complications of therapy and of INH prophylaxis. METHODS: This study is a retrospective review of the records of 880 renal transplant recipients in two centers in Turkey. RESULTS: Tuberculosis developed in 36 patients (4.1%) at posttransplant 3-111 months, of which 28 were successfully treated. Eight patients (22.2%) died of tuberculosis or complications of anti-tuberculosis therapy. Use of rifampin necessitated a mean of 2-fold increase in the cyclosporine dose, but no allograft rejection occurred due to inadequate cyclosporine levels. Hepatotoxicity developed in eight patients during treatment, two of whom died due to hepatic failure. No risk factor, including age, gender, renal dysfunction, hepatitis C, or past hepatitis B infection, was found to be associated with development of hepatic toxicity. A subgroup of 36 patients with a past history of or radiographic findings suggesting inactive tuberculosis, was considered to be at high risk for developing active disease, of whom 23 were given isoniazid (INH) prophylaxis. None versus 1 of 13 (7.7%) of cases with and without INH prophylaxis, respectively, developed active disease (P>0.05). None of the patients receiving INH had hepatic toxicity or needed modification of cyclosporine dose. CONCLUSIONS: These data show that tuberculosis has a high prevalence in transplant recipients, that it can effectively be treated using rifampin-containing antituberculosis drugs with a close follow-up of serum cyclosporine levels, and that INH prophylaxis is safe but more experience is needed to define the target population.     

Somatostatin infusion withdrawal in the diagnosis of childhood growth hormone deficiency

OBJECTIVE: An evaluation of growth hormone (GH) testing for GH deficiency (GHD) in childhood is confounded by the lack of a world-wide consensus on the definition of GHD. Although a single GH test remains the most powerful biochemical tool in the evaluation of a child with growth failure, the test remains far from ideal. Withdrawal of somatostatin (SS) infusion is followed by a rebound rise of GH thought to be mediated by endogenous GH-releasing hormone (GHRH) function. This study was designed to compare the GH response to 90 min SS infusion in children with normal GH secretion versus children with GH deficiency. METHODS: Ten children with GHD and 10 healthy controls (NC) have been evaluated for GH response to somatostatin infusion withdrawal (SSIW) and compared with response of two provocative tests, glucagon plus propranolol test and L-Dopa test. All children received constant infusion of somatostatin for 90 min (3 microg/kg per h, Stilamin, Serono, Aubonne, Switzerland). In order to determine GH, blood samples were obtained 90 min before the SS infusion and 0, 15, 30, 45, 60, 75, and 90 min after the cessation of infusion. RESULTS: Growth hormone peak levels with SSIW were significantly lower in GH deficient children than in healthy children (2.5 +/- 1.2 ng/dL, vs 21.9 +/- 5.3 ng/dL, respectively, P < 0.01). No adverse effects were observed during or after somatostatin infusion. CONCLUSION: In the present study, SSIW elicited a significant GH rise in healthy children but not in children with GH deficiency. Although further controlled studies using more data are necessary to expand these findings, the results suggested that children with GH deficiency can be reliably discriminated from healthy children by SSIW.     

Rapid multi‐echo measurement of brain metabolite T2 values at 7 T using a single‐shot spectroscopic Carr–Purcell–Meiboom–Gill sequence and prior information

We present a method for the robust and accurate estimation of brain metabolite transverse relaxation times (T₂) from multiple spin‐echo data acquired with a single‐shot Carr–Purcell–Meiboom–Gill (CPMG) spectroscopic sequence. Each acquired echo consists of a small number of complex time‐domain data points. The amplitudes of the spectral components in each echo are calculated by solving a set of linear equations in which previously estimated frequencies and linewidths serve as prior information. These priors are obtained from a short MRS experiment in which a large number of time‐domain data points are acquired, and are subsequently estimated using linear prediction with singular value decomposition (LPSVD) processing. We show that this process can be used to accurately and rapidly measure the T₂ values for the main singlet resonances in single‐volume MRS measurements in the brain. The proposed method can be generalized to any set of MRS experiments comprising repeated measurements of amplitude changes, e.g. as a function of an experimental parameter, such as TE, inversion time or diffusion weighting. Copyright © 2013 John Wiley & Sons, Ltd.     

The influence of bilateral sagittal split ramus osteotomy on submental‐cervical aesthetics

The effect of orthodontic‐surgical treatment on submental‐cervical region was evaluated in a very limited number of studies. The aim of this study was to evaluate submental‐cervical soft tissue contour changes following mandibular advancement and set‐back procedures via bilateral sagittal split ramus osteotomy. Sixty‐seven patients were included in this study. Group 1 consisted of 27 skeletal Class II patients who underwent mandibular advancement surgery, whereas Group 2 consisted of 40 skeletal Class III patients who underwent mandibular set‐back surgery. Various linear and angular measurements were performed on pre‐operative and sixth month post‐operative cephalometric radiographs. A new method was used to evaluate the amount of sagging at submental region. The submental length did not change in Group 1; however, it decreased significantly in Group 2 (P < 0·05). The angle between submental plane and facial plane decreased to 95·9° from 98·8° in Group 1(P < 0·05), whereas it increased to 93·1° from 88·2° in Group2 (P < 0·05). The change of submental soft tissue sag was almost stable in Group 1, while 0·34 mm increase of sag was observed in Group 2. This increase was not statistically significant (P > 0·05). Mandibular set‐back and advancement procedures do not remarkably change the submental sag following approximately 6 mm jaw movement. Although mandibular advancement did not significantly effect submental length, soft tissue followed mandibular set‐back with a ratio of 1:1 at C‐point to projection of soft tissue pogonion and 1:0·7 at C‐point to soft tissue menton distances.     

The impact of managers' perceptions of learning organizations on innovation in healthcare: sample of Turkey

Organizational learning is the process of increasing effective organizational activities through knowledge and understanding. Innovation is the creation of any product, service or process, which is new to a business unit. Significant amount of research on organizational learning place a central meaning on the fact that there is a positive relationship between organizational learning and innovation. Both organizational learning and innovation are essential for organizations to prepare for change. The aim of this study is to determine to what extent the identified learning organization dimensions are associated with innovation. The study used a quantitative non‐experimental design employing statistical analysis via multiple regression and correlation methods to identify the relationships between the variables examined. Because the research was conducted in a non‐experimental way, learning organization dimensions are referred to as predictor variables, and innovation is referred to as the criterion variable. Watkins and Marsick's Dimensions of the Learning Organization Questionnaire was used in the study. Questionnaires were distributed to 498 hospital managers and, 243 valid responses were used in this study. Therefore, 243 hospital managers working at 250 Ministry of Health (public) hospitals across Turkey participated in the study. Results demonstrate that there are significant and positive correlations between learning organization dimensions and innovation. Intercorrelations between learning organization dimensions and correlations between learning organization dimensions and innovation were average and high, respectively. Results further indicate that the dimensions of the learning organizations explained 66.5% of the variance for the innovation. Copyright © 2012 John Wiley & Sons, Ltd.