An insulin-like growth factor II (IGF-II) affinity-enhancing domain localized within extracytoplasmic repeat 13 of the IGF-II/mannose 6-phosphate receptor

Insulin-like growth factor II (IGF-II) and phosphomannosylated glycoproteins bind to distinct sites on the same receptor, the IGF-II/mannose 6-phosphate receptor (IGF2R). Analysis of truncated receptors (minireceptors) has been used to map the IGF-II binding site within the receptor's extracytoplasmic domain, which consists of 15 homologous repeats. A minireceptor consisting of repeat 11 contained the minimal elements for binding IGF-II, but with 5- to 10-fold lower relative binding affinity than the full-length receptor. We hypothesized that the complete, high-affinity IGF-II binding site is formed by interaction between the primary site in repeat 11 and a putative affinity-enhancing domain. To determine the minimum portion of the IGF2R's extracytoplasmic domain needed for expression of high-affinity IGF-II binding, a nested set of FLAG epitope-tagged minireceptors encompassing repeats 11 through 15 was prepared and transiently expressed in 293T cells. Minireceptors containing repeats 11-13 or 11-15 exhibited high affinity, comparable to the full-length receptor (IC50 = 1-2 nM), whereas constructs containing repeat 11 only or repeats 11-12 did not (IC50 = 10-20 nM). These data suggested that the affinity-enhancing domain is located within repeat 13, which contains a unique 43-residue insert that has approximately 50% sequence identity to the type II repeat of fibronectin. Although a repeat 13 minireceptor did not bind IGF-II on its own, an 11-13 minireceptor containing a deletion of the 43-residue insert exhibited low IGF-II binding affinity (IC50 = 10-20 nM). Expression of mutant receptors from a full-length IGF2R construct bearing a deletion of the 43-residue insert was very low relative to wild type. Depletion assays using IGF-II-Sepharose showed that the mutant receptor had lower affinity for IGF-II than the wild-type receptor. This study reveals that two independent receptor domains are involved in the formation of a high-affinity binding site for IGF-II, and that a complete repeat 13 is required for high-affinity IGF-II binding.     

Androgen and sleep-related erections

BACKGROUND: Nonspecific esophageal motility disorder (NEMD) represents a difficult therapeutic challenge because of the heterogeneous nature of the esophageal motor functions. We studied the effects of cisapride on the esophageal symptoms and esophageal motor function in a group of patients with NEMD showing delayed esophageal transit. METHODS: Seventy eligible patients were entered into a 4-week, double-blind randomized comparison of 10 mg of cisapride or placebo, four times daily. Symptom assessment, esophageal manometry after wet swallows, and esophageal scintigraphy after intake of a liquid and solid bolus were performed in each patient before and after treatment. RESULTS: After 4 weeks of treatment cisapride significantly increased the prevalence of esophageal peristaltic contractions (percentage of total contractions, P < 0.05 versus base line and placebo) and significantly improved esophageal emptying of the solid bolus (P < 0.05 versus placebo) but not of the liquid bolus. Placebo did not have any significant effects versus base line on these variables. Both placebo and cisapride improved the distal esophageal amplitude versus base line (no significant intergroup differences). Symptom scores were significantly reduced after 4 weeks of treatment versus base line in both groups (no significant intergroup differences except for heartburn and regurgitation, P < 0.05). On global evaluation of treatment, significantly more patients in the cisapride group were rated as markedly or moderately improved, when compared with placebo. CONCLUSIONS: The results of the present study showed that cisapride is effective and well tolerated in patients with NEMD accompanied by delayed esophageal transit. Symptomatic improvement may possibly be related to its beneficial action on the esophageal body by increasing the number of peristaltic contractions and esophageal emptying of solids.     

Silizium — Mikrotechnik für thermische Sensoren

Recent developments in the fields of thin film technology processes and silicon micromachining results in thermal sensors with astonishing specifications. Evaporated germanium thermistors placed on membranes of CVD silicon nitride which in turn are fixed at micromachined silicon substrates can act as extremely sensitive thermometers, IR radiation detectors, flow sensors for liquid and gaseous media and sensors for acoustic flow, for example. This paper presents some results of the relevant work at the department of electrical engineering Vienna University of Technology.     

Bronchiolitis obliterans organizing pneumonia

Bronchiolitis obliterans organizing pneumonia (BOOP) is increasingly recognized as an important cause of diffuse infiltrative lung disease. It is a diagnostic consideration in patients with a febrile flu-like illness of a few weeks' duration and a roentgenogram showing bilateral patchy infiltrates that are not responsive to a typical course of antibiotics. It is defined as granulated tissue plugs within lumens of small airways that extend into alveolar ducts and alveoli. Clinically, a flu-like illness, cough, and crackles are common. Pulmonary function studies of patients show a decreased vital capacity, normal flow rates (except in smokers), and a decreased diffusing capacity. It is generally idiopathic, but it may occur during the resolution of a viral or mycoplasma pneumonia. It is also associated with a variety of systemic illnesses and clinical settings. These include the connective tissue disorders, antineoplastic and other drugs, and immunological disorders, as well as bone marrow and lung transplantation. There are numerous related disorders, including human immunodeficiency virus infection, radiation therapy, thyroiditis, and alcoholic cirrhosis. In idiopathic BOOP, complete resolution occurs in 65% to 85% of patients treated with corticosteroid therapy. This type of therapy is often effective in patients with associated systemic disorders or in other clinical settings, but there may be limited or no response in patients with dermatomyositis, immunosuppression, or interstitial opacities at the lung bases. Respiratory failure leading to death may occur in 5% of patients. It is important to add BOOP to the differential diagnosis of febrile, noninfectious illnesses that are mimics of pneumonia.     

Mycosis fungoides palmaris et plantaris

BACKGROUND: Mycosis fungoides primarily localized to the palms and soles is rare and has been previously reported as cutaneous lymphoma in four patients or as Woringer-Kolopp disease in eight patients. OBSERVATIONS: Four patients were initially diagnosed and treated unsuccessfully for various palmoplantar dermatitides until histopathologic findings revealed mycosis fungoides. Each case exhibited a clonal rearrangement of T-cell receptor gamma genes and immunohistochemical studies consonant with mycosis fungoides. All patients had limited skin involvement without evidence of extracutaneous involvement. CONCLUSIONS: Mycosis fungoides palmaris et plantaris is an uncommon expression of mycosis fungoides that manifests primarily on the palms and soles and clinically may mimic various inflammatory palmoplantar dermatoses. A biopsy is recommended in the evaluation of recalcitrant palmoplantar dermatoses.     

Application of canonical transformation with missing values to multitrait evaluation of Jersey type

A multitrait animal model was used to calculate predicted transmitting ability and reliabilities for final score and 15 linear type traits of 225,632 US Jersey cows. Records were adjusted for age and stage of lactation before analysis. The model contained effects for interactions of herd and date scored; year scored, parity, and age; and herd and sire; effects of permanent environment and additive genetics were also included. Of the 381,511 records included, some observations were missing for final score (8%), body depth (43%), and teat length (33%). The evaluation system used a canonical transformation, included several random effects, and estimated missing values with each iteration. Inbreeding was considered in the computations. Convergence was achieved in approximately 50 rounds of iteration. Correlations between animal and sire model predicted transmitting ability ranged from 0.56 to 0.95 and generally were higher for bulls than for cows and for more recent birth years. Genetic trend was strongly positive for dairy form, final score, and rear udder traits (height and width) and negative for udder depth. For other traits, genetic trend was small. This methodology should improve the accuracy of genetic evaluations for type traits of US Jerseys.     

Study of the action of tamoxifen on the mammary gland epithelium of premenopausal patients by lysosome quantification

Tamoxifen is an antiestrogen drug widely utilized for the adjuvant hormonal treatment of breast carcinoma. Its use in the primary prophylaxis of this disease is currently being proposed. Although the drug has few side effects, its precise action on breast tissue that has not undergone neoplastic transformation has not been fully elucidated. This prospective, randomized study assessed the estrogen activity of tamoxifen on the mammary gland epithelium of premenopausal patients using a quantitative analysis of mammary epithelium lysosome identified by the cytochemical technique of GOMORI for acid phosphatase and by light microscopy. Tamoxifen significantly increased the number of lysosomes only during the secretory phase of the menstrual cycle. We concluded that the early effect of the drug on normal mammary tissue is synergistic with the effect of estrogen during the premenopausal period.     

Stereotactic transcranial magnetic stimulation: correlation with direct electrical cortical stimulation

OBJECTIVE: To evaluate stereotactic transcranial magnetic stimulation (TMS) as a tool for presurgical functional mapping of human motor cortex. METHODS: Transcranial magnetic stimulation using a frameless stereotactic system was performed in two patients with tumors near the central sulcus. TMS motor function maps were plotted on the patients' three-dimensional volumetric magnetic resonance imaging data and compared with direct electrical cortical stimulation at surgery with the patient under local anesthesia. RESULTS: Stereotactic TMS was well tolerated by both patients and was consistent with known somatotopic representation of human motor cortex. The results demonstrated a good correlation between the TMS and electrical cortical stimulation maps, with all TMS responses eliciting more than 75% of the maximum motor evoked potential falling within 1 cm of the electrical cortical stimulation site. CONCLUSIONS: Our findings indicate that stereotactic TMS is feasible and can provide accurate noninvasive localization of cortical motor function. It may prove to be a useful method for presurgical planning.