Osteoma cutis in pseudohypoparathyroidism.

Pseudohypoparathyroidism (PHP) is a hereditary disorder characterized by an end-organ resistance for parathormone. PHP can be classified into different types by biochemical and phenotypic characteristics and the level of the defect in the hormone-receptor complex. PHP is described as Albright's hereditary osteodystrophy (AHO) when a specific phenotype is present. We report a case of osteoma cutis in a 30-year-old woman with AHO. Successful treatment was obtained by debriding the lesion followed by split-thickness skin grafting.     

Monoclonal anti-idiotype antibodies in immunotherapy of ovarian carcinoma (MAb ACA125) and breast carcinoma (MAb ACA14C5)]

Anti-idiotypic antibodies, which imitate a tumor-associated antigen by their variable region, offer an elegant method for the induction of a specific immune response, when used as a surrogate antigen for immunization. We generated anti-idiotypic antibodies imitating 2 different tumor-associated antigens. I. CA125 for ovarian carcinomas and II. 14C5, a tumor-associated cell substrate adhesion molecule on breast cancer cells, whereas the first approach could be introduced in a first clinical trial and the second was evaluated in an immunocompetent animal model. For the induction of an immune response against CA125, 18 patients with advanced ovarian cancer (n = 6) or heavily pretreated recurrences (n = 12) were immunized with the anti-idiotypic antibody MAb ACA125. Patients were treated with 2 mg anti-idiotype antibody every two weeks for 4 injections i.m. and then monthly. 12 of 18 patients demonstrated an anti-anti-idiotypic (Ab3) response, which was to a lower extent also directed against CA125 and 9 of 18 patients developed a CA125 specific cellular immune response by their peripheral blood lymphocytes. Based on this data a follow-up clinical trial in advanced ovarian cancer patients with minimal residual disease in an adjuvant approach after primary therapy was started to evaluate the effect of the immune response on the progression free survival. For immunotherapy of breast cancer, we generated a murine monoclonal anti-idiotypic antibody (MAb ACA14C5), which imitates a cell substrate adhesion molecule on breast cancer cells. The anti-idiotype was introduced in an immunocompetent animal to prove his capability on induction of an immune and tumor response. The results showed a highly significant difference in the tumor growth of the ACA14C5 treated group in contrast to the controls starting the immunization on day 6 after tumor cell application with 10 of 12 animals being cured from their tumor burden. Prophylactic immunization against the invasion antigen of breast cancer by anti-idiotypic antibodies showed protection against increasing tumor burden. However, in the situation of established tumors only minor responses could be detected. Vaccination with anti-idiotypic antibodies comprises an effective method for induction of a specific immune response against non-immunogenic tumor-associated antigens and should be therefore considered in immunological approaches to tumor therapy, where the primary structure and sequence of the antigen, e.g. CA125, is up to now not available.     

Changes in the expression of alpha(2)-adrenergic receptor subtypes during maturation of neuronal cells from fetal pig superior cervical ganglia.

The expression of presynaptic alpha(2)-adrenergic receptor (alpha(2)-AR) subtypes was investigated in cultured neurons from fetal pig superior cervical ganglion (SCG). Cells were incubated with chicken antibodies against alpha(2)A-, alpha(2)B- or alpha(2)C-AR subtypes either alone or together with antibodies against dopamine-beta-hydroxylase (DbetaH, a marker for adrenergic neurons) or against choline acetyl transferase (ChAT, a marker for cholinergic neurons). We found immunoreactivity for all three alpha(2)-AR subtypes in SCG-cells when cultured for 8-11 days. The relative expression of the alpha(2)A-subtype was approximately 1/3 of that of alpha(2)B- and alpha(2)C-AR. Co-localisation of all three alpha(2)-AR subtypes was observed in cells expressing DbetaH or ChAT. Increasing the potassium concentration in the culture medium increased the expression of DbetaH and decreased the expression of the alpha(2)A- and alpha(2)C-subtype without altering the expression of the alpha(2)B-subtype. Co-culture of neurons with pig splenocytes enhanced the expression of ChAT and decreased the expression of the alpha(2)B-subtype without altering the expression of alpha(2)A- and alpha(2)C-subtypes. Our results indicate that the three alpha(2)-receptor subtypes are expressed on both noradrenergic and cholinergic nerves. Induction of the noradrenergic phenotype favours the expression of the alpha(2)B-subtype over that of the alpha(2)A- and alpha(2)C-subtype. Conversely, enhancement of the cholinergic phenotype favours the expression of the alpha(2)A- and alpha(2)C-subtypes over that of the alpha(2)B-subtype. Our results suggest that the alpha(2)B-receptor is preferentially associated with noradrenergic nerve endings.     

Concentration-dependent effects of muscimol to enhance pulsatile GnRH release from GT1–7 neurons in vitro

Immortalized GT1–7 neurons were used to characterize the effect of muscimol, a GABA_A receptor agonist, to enhance pulsatile gonadotropin-releasing hormone (GnRH) release. GT1–7 neurons were grown on Cytodex-3 beads and placed in special superfusion microchambers. The cells were superfused at a rate of 6.2 ml·h⁻¹ with Media 199 (pH 7.35) using a commercially available perfusion system. After a pre-muscimol period of 120 min, the cells were exposed for 5 min to 0.35, 1, 5 or 10 μM muscimol or 5 μM muscimol+20 μM of the GABA_A receptor antagonist, bicuculline. Following removal of the muscimol (and bicuculline, in the case of the latter experiment), the superfusion was continued for another 115 min. Sample fractions were collected at 5 min intervals throughout the perfusion. Basal GnRH release from the GT1–7 neurons was pulsatile with an average interpulse interval of 45.4±0.5 min and an average pulse amplitude of 191.5±22.6 pg·min·ml⁻¹. Our results also demonstrated that the GABA_A receptor agonist, muscimol, enhances pulsatile GnRH release from GT1–7 neurons in culture. The response to muscimol was saturable and concentration-dependent with an EC₅₀ of 0.47 μM. The effects of 5 μM muscimol to increase GnRH pulsatility were blocked by co-exposure to the GABA_A receptor antagonist, bicuculline. The average GnRH interpulse intervals were 41.7±1.8 min, 32.5±2.9 min, 30.6±0.7 min and 25.5±0.4 min in the period following exposure to 0.35, 1, 5 and 10 μM of muscimol, respectively (post-muscimol period). GnRH pulse amplitude (mean-area for each pulse) was increased during exposure to muscimol but not during the pre- or post-muscimol periods. The GABA_A receptor antagonist, bicuculline, itself had no effect on pulsatile GnRH release. These results are consistent with previously published reports suggesting that activation of the GABA_A receptor stimulates hypothalamic GnRH release in embryonic and neonatal animals.     

B7-1和IL-12基因转染对肝癌细胞免疫原性的影响

目的 观察Ｂ７－１和ＩＬ－１２基因表达对人肝癌细胞免疫原性原影响。方法 分别将Ｂ７－１和ＩＬ－１２基因以逆转录病毒介导转染ＨｅｐＧ２细胞。阳性克隆细胞与健康人外周血淋巴细胞（ＰＢＬ）混合培养后,用流式细胞仪检测ＰＢＬ表面Ⅰ类人白细胞抗原（ＨＬＡ－Ⅰ）分子表达,以ＭＴＴ法检测ＰＢＬ的特异性杀伤活性Ｋ５６２细胞的活性。结果 混合ＨｅｐＧ２／Ｂ７－１ＨｅｐＧ２／ＩＬ－１２细胞组ＰＢＬ表面的ＨＬＡ－Ⅰ分子     

Tobacco use and colon cancer

Smoking cigarettes has been consistently associated with adenomatous polyps. However, only a few studies have reported associations between smoking cigarettes or using other forms of tobacco and colon cancer. A population-based case-control study of colon cancer was conducted in 3 areas in the United States: northern California, Utah and Minnesota. We observed approximately a 50% increase in colon cancer risk from smoking over a pack of cigarettes per day among both men and women. Those who stopped smoking remained at increased risk, even if they stopped over 10 years ago. Our data suggest that the amount smoked may be a more important factor than the total number of years smoked. Smoking neither cigars nor pipes was associated with an increased risk of colon cancer. Among female participants only, those who smoked over 20 cigarettes per day and had a large body mass index were at greater risk of colon cancer than participants who smoked the same amount but were smaller (p for interaction among women = 0.04). Int. J. Cancer, 70:259–264, 1997. © 1997 Wiley-Liss, Inc.     

Systematic review and meta‐analysis of psychological interventions in people with diabetes and elevated diabetes‐distress

Aims

The clinical relevance of diabetes‐distress is increasingly recognized, but little is known about the efficacy of interventions specifically targeted to treat elevated diabetes‐distress. Therefore, this systematic review sought to determine the efficacy of psychological interventions aimed at treating elevated diabetes‐distress in people with Type 1 or Type 2 diabetes.

Methods

We systematically searched literature from five databases. Randomized controlled trials (RCTs) with an English abstract, describing the results of a psychological intervention in adults with diabetes were included. Articles were eligible for inclusion if the primary outcome was diabetes‐distress measured by the Problem Areas in Diabetes Scale (PAID‐5/PAID‐20) or the Diabetes Distress Scale (DDS‐17). Only mean group diabetes‐distress values above cut‐off at baseline or the results of a subgroup above cut‐off (PAID‐5 ≥ 8, PAID‐20 ≥ 40 or DDS‐17 ≥ 3) were included.

Results

The search yielded 8907 articles. After removing 2800 duplicates, 6107 articles remained. Titles and abstracts were screened, leaving 394 potential articles of interest, nine of which were RCTs. In a random‐effects meta‐analysis, the pooled effect size for diabetes‐distress was 0.48 (Cohen's d), Z = 3.91, P < 0.0001. Statistical heterogeneity was I² = 46.67% (confidence intervals 45.06% to 48.28%). Diabetes‐tailored psychological interventions reduced HbA_1c (Cohen's d = 0.57), whereas mindfulness‐based interventions did not (Cohen's d = 0.11).

Conclusions

This systematic review shows that specifically diabetes‐tailored psychological interventions are effective in reducing elevated diabetes‐distress and HbA_1c. More rigorous studies are warranted to establish the full potential of these interventions. PROSPERO database registration ID: CRD42017075290.