Cell origin in experimental repair of cricoid cartilage defects treated with recombinant human bone morphogenetic protein-2

We determined the origin of new cartilage and new bone induced by recombinant human bone morphogenetic protein-2 (rhBMP-2) at the site of cricoid cartilage defects in rabbits randomly divided into eight groups. The cricoid cartilage was split vertically along the anterior midline and a strip was excised from the anterior part of the cricoid cartilage in all rabbits. The perichondrium from the anterior part of the cricoid cartilage was trimmed off in four groups; two groups treated with rhBMP-2 and two control groups. In four other groups, the anterior perichondrium was detached and used as a flap with two groups treated with rhBMP-2 and two groups serving as controls. The rabbits were killed 1 week or 4 weeks after surgery. The larynges were removed, fixed and sectioned, and the sections were stained for light microscopy using various cytochemical and immunological techniques. New cartilage was only present close to the host perichondrium adherent to cricoid cartilage in rabbits treated with rhBMP-2. New bone was present 4 weeks after surgery, although calcified matrix and alkaline phosphatase activity could be detected at the site of cricoid defects as early as 1 week after surgery. The cell proliferation marker Ki-67 was strongly expressed in granulation tissue and bone marrow, and it was moderately expressed in muscles adjacent to the cricoid cartilage in rhBMP-2-treated specimens. BMP receptors were strongly expressed in cartilage and moderately expressed in adjacent muscles. We conclude that new cartilage originates from the mesenchymal progenitor cells of host perichondrium adherent to cricoid cartilage in rabbits treated with rhBMP-2. New bone may originate from local muscle.     

Genetic services for men: the preferences of men with a family history of prostate cancer.

PURPOSE: Men have a lower uptake of genetic services than women; however, the specific needs and preferences of men at risk of genetic conditions other than hereditary breast ovarian cancer are not known. We ascertain the information preferences of men with a family history of prostate cancer. METHODS: Unaffected men and their partners were administered a written questionnaire. RESULTS: Responses were received from 280 men (response rate: 59.2%) and 174 partners (response rate: 74%). Most men (59.6%) reported having insufficient information about their risk and wanted further information about personal risk (93.2%) and risk management (93.6%). Strikingly, 56.3% preferred to receive information related only to positive outcomes. Urologists were the preferred source of information, but there was considerable interest in a multidisciplinary service approach significantly associated with the number of affected relatives (odds ratio = 1.94, P < .002). Partners' level of concern was not associated with interest in multidisciplinary services, satisfaction with information, or support received. CONCLUSIONS: Delivering services to men at risk will require a multifaceted approach by primary care providers and specialists. Challenges include meeting men's expectations in the face of uncertain medical knowledge, engaging those at high risk in multidisciplinary services, and delivering tailored information to those at lower risk.     

Gastric and duodenal mucosa in ''healthy'' individuals. An endoscopic and histopathological study of 50 volunteers.

The results of histological and immunohistochemical examination of gastric and duodenal biopsy specimens from 50 volunteers without a clinical history of gastrointestinal disease are reported. Multiple specimens of tissue from standard sites in the stomach and duodenum were carefully orientated, and serially sectioned for examination by light microscopy and for immunohistochemical characterisation of plasma cells within the lamina propria. The antrum and fundus were normal in 32 of the 50 subjects but the other 18 showed histopathological evidence of gastritis in either the antrum or fundus. The latter appeared to be age-related. There was considerable variation in the appearance of the surface epithelium of the duodenum within as well as among individual subjects. Superficial gastric metaplasia in one or more biopsy specimens from the duodenal bulb was found in 64% of individuals. Histopathological examination of the duodenum revealed signs of chronic inflammation in 12% of the subjects. In two individuals there was active inflammation but in only one of these was the diagnosis made on endoscopic appearances. Histological criteria important for the diagnosis of duodenitis are discussed. The number of plasma cells in different biopsy specimens from subjects not showing histological signs of inflammation was variable. The ratio IgA:IgG:IgM producing plasma cells was remarkably constant from subject to subject as well as from specimen to specimen.     

Monitoring serum CEA in women with primary breast tumours positive for oestrogen receptor and with spread to lymph nodes.

Serum carcinoembryonic antigen concentrations (serum CEA) in 80 patients with primary breast cancer were measured preoperatively, one month after operation, and thereafter serially every third month. These data were related to histological and morphometric features of the primary breast carcinoma and the lymph node metastases and to clinical follow up data. Analysis of the serum CEA values showed significant correlations with size of tumour, the presence of lymph node metastases, oestrogen receptor, and occurrence of distant metastases. Furthermore, the results indicated that serial determination of serum CEA in the first two years after operation may be useful in monitoring for the occurrence of distant metastases in patients with metastatic spread to lymph nodes and with large (greater than or equal to 2 cm) primary breast tumours positive for oestrogen receptor. In agreement with other studies, however, it was found that the predictive value of serum CEA concentrations in general is weak and costs may prohibit the implementation of the routine assessment of CEA concentrations.     

Vilse, a conserved Rac/Cdc42 GAP mediating Robo repulsion in tracheal cells and axons

Slit proteins steer the migration of many cell types through their binding to Robo receptors, but how Robo controls cell motility is not clear. We describe the functional analysis of vilse, a Drosophila gene required for Robo repulsion in epithelial cells and axons. Vilse defines a conserved family of RhoGAPs (Rho GTPase-activating proteins), with representatives in flies and vertebrates. The phenotypes of vilse mutants resemble the tracheal and axonal phenotypes of Slit and Robo mutants at the CNS midline. Dosage-sensitive genetic interactions between vilse, slit, and robo mutants suggest that vilse is a component of robo signaling. Moreover, overexpression of Vilse in the trachea of robo mutants ameliorates the phenotypes of robo, indicating that Vilse acts downstream of Robo to mediate midline repulsion. Vilse and its human homolog bind directly to the intracellular domains of the corresponding Robo receptors and promote the hydrolysis of RacGTP and, less efficiently, of Cdc42GTP. These results together with genetic interaction experiments with robo, vilse, and rac mutants suggest a mechanism whereby Robo repulsion is mediated by the localized inactivation of Rac through Vilse.     

Chromatin interactions in differentiating keratinocytes reveal novel atopic dermatitis– and psoriasis-associated genes

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Parietal cell protrusions and fundic gland cysts during omeprazole maintenance treatment

Parietal cell protrusion (PCP), swelling and bulging of parietal cells, has been observed in the oxyntic mucosa of patients receiving omeprazole. The frequency of this event and the underlying mechanisms remain to be clarified. As such, it is unknown whether there is a relation with either serum gastrin or Helicobacter pylori infection, and whether PCP predisposes to the development of fundic gland cysts (FGC). We therefore investigated the development of PCP and FGC in gastroesophageal reflux disease (GERD) patients treated with omeprazole and correlated findings to duration of therapy, gastrin, and H pylori infection. In a randomized, double-blinded study, GERD patients were evaluated by endoscopy with biopsy sampling for histology and culture at baseline, and after 3 and 12 months' therapy with omeprazole 40 mg daily. H pylori-positive patients were randomized to additional eradication therapy or placebo antibiotics at baseline. All histological slides were scored blinded for time and outcome of culture for the presence of PCP and FGC. Fasting serum samples from all visits were used for gastrin measurements. The prevalence of PCP increased during omeprazole therapy from 18% at baseline to 79% and 86% at 3 and 12 months (P < .001, baseline v both 3 and 12 months). The prevalence of FGC increased from 8% to 17% and 35% (P < .05, baseline v 12 months). The prevalence of PCP and FGC did not differ among the H pylori-positive and H pylori-negative patients at baseline (PCP 16% v 20% and FGC 7% v 8%, respectively). Whereas H pylori eradication did not significantly affect development of PCP (P = .7), FGC developed significantly more often in the H pylori-eradicated patients when compared with persistent H pylori-positive patients (P < .05). PCP development was related to serum gastrin rise during therapy. In conclusion, PCP occurs in most patients within the first months of omeprazole treatment and is related to increased gastrin levels. FGC develops more gradually and is enhanced by H pylori eradication.     

Effect of depolarizing and hyperpolarizing agents on the membrane potential difference of primary cultures of rabbit aorta vascular smooth muscle cells

Vascular smooth muscle cells of rabbit aorta were enzymatically dispersed, kept in primary culture, and studied between days 1 and 7 in a bath rinsed with Ringer-like solution at 37°C. The electrical membrane potential difference (PD) was measured with microelectrodes. The mean value of PD was –50±0.4 mV (n=53). Cromakalim (BRL 34915), 1 mol/l and 10 mol/l, hyperpolarized the membrane potential by 9±1 mV (n=11) and 15±1 mV (n=53) respectively. Glibenclamide (10 mol/l) abolished the hyperpolarizing effect of cromakalim (n=6). Simultaneous addition of cromakalim and glibenclamide (both 10 mol/l, n=11) and glibenclamide itself (10 mol/l, n=7) had no effect on PD. In patch-clamp experiments in outside-out-oriented Ca²⁺-sensitive K⁺ channels, cromakalim increased the open probability (P _o) only slightly and only with a cytosolic Ca²⁺ activity of 1 mol/l. In all other series cromakalim had no effect on the P _o of these channels. Forskolin (10 mol/l) hyperpolarized PD by 6±1 mV (n=13). The nucleotides UTP, ATP and ITP (10 mol/l) depolarized PD by 12±1 mV (n=7), 8±1 mV (n=65) and 5±1 mV (n=6) respectively. GTP, [,-methylene]ATP and adenosine had no significant effect. Mn²⁺ (1 mmol/l, n=18), Ni²⁺ (1 mmol/l, n=13), Co²⁺ (1 mmol/l, n=11), Zn²⁺ (1 mmol/l, n=6) and the Ca²⁺-channel blockers verapamil and nifedipine (both 0.1 mmol/l, n=6) did not attenuate the depolarization induced by 10 mol/l ATP. Fetal calf serum (100 ml/l, n=7) depolarized PD by 11±2 mV. This effect was not abolished by nifedipine or by replacing NaCl by choline chloride. The data indicate that PD of vascular smooth muscle cells is depolarized by P₂ agonists and hyperpolarized by the K⁺-channel opener cromakalim. The effect of cromakalim is antagonized by glibenclamide. The effect of cromakalim is probably not mediated by the K⁺ channel identified in excised patches.Supported by DFG Gr 480/10     

Structural study of compounds modelling elementary polymer units, 6. X-ray structural and quantum-chemical investigation of the cis- and trans-isomeric models of the polynaphthoylenebenzimidazole elementary units

The X-ray structural investigation of the naphthoylenebis-(benzimidazole) ( 1 ) cis- and trans-isomers as models for the cis and trans elementary units of the corresponding poly(naphthoylene-benzimidazoles) (PNBI) was carried out. The correctness of the previous identification of the isomers was confirmed, and exact geometrical parameters of the PNBI elementary units (required, in particular, for the calculation of the Kuhn segment of PNBI) were determined. Quantum-chemical semi-empirical calculations of the ground and excited electronic states of the isomers were carried out. Both experimental and theoretical data confirm a larger stability of the planar π-conjugated structure of the trans-isomer in comparison with the cis-isomer in the ground as well as in the excited electronic state. Crystals of the cis- and trans-isomers obtained from trifluoroacetic acid solutions are the solvates of bis(trifluoroacetates) of diprotonated 1 with an extremely high content of the solvating trifluoroacetic acid. This peculiarity is favourable for modelling the main characteristics of the interaction between PNBI and protonic polar solvent molecules, viz. preferred types of H-bonding and a possibility of interaction of the electronic lone pairs of the solvent molecules with the π-electronic systems of the elementary units of PNBI by charge transfer complexes.     

Associations of Mediterranean diet with psychological ill-being and well-being throughout the pregnancy course: The GESTAFIT project

Quality of Life Research - The relation between diet and maternal mental health during pregnancy might be relevant to prevent adverse materno-foetal outcomes. This study examined the association of...