Dopamine inhibition of anterior pituitary adenylate cyclase is mediated through the high-affinity state of the D2 receptor

The diterpinoid forskolin stimulated adenylate cyclase activity (measured by conversion of [³H]-ATP to [³H]-cAMP) in anterior pituitary from male and female rats. Inhibition of stimulated adenylate cyclase activity by potent dopaminergic agonists was demonstrable only in female anterior pituitary. The inhibition of adenylate cyclase activity displayed a typically dopaminergic rank order of agonist potencies and could be completely reversed by a specific dopamine receptor antagonist. The IC₅₀ values of dopamine agonist inhibition of adenylate cyclase activity correlated with equal molarity with the dissociation constant of the high-affinity dopamine agonist-detected receptor binding site and with the IC₅₀ values for inhibition of prolactin secretion. These findings support the hypothesis that it is the high-affinity form of the D₂ dopamine receptor in anterior pituitary which is responsible for mediating the dopaminergic function of attenuating adenylate cyclase activity.     

An adenosine kinase mutation in baby hamster kidney cells causing increased sensitivity to adenosine

A class of aravinosyladenine (araA)-resistant mutants of baby hamster kidney (BHK 21/C13) cells exhibits multiple phenotypes: resistance to araA and deoxyadenosine, extreme sensitivity to adenosine (Ado) and varying degrees of deficiency in adenosine kinase (AK) activity. One of these Ado^s/araA^r strains, ara-S10d, was isolated without mutagenesis and was shown to possess about 59% level of the wild-type AK activity. The AK from ara-S10d had an altered K_m and pH optimum and was stimulated by K⁺ cations. A number of Ado^s to Ado^r revertants were isolated from araS10d, and in all of the 7 examined, the AK activity was reduced to a nondetectable level. The altered kinetic parameters of the AK enzyme in ara-S10d cells suggest a mutation of the AK gene that leads to the synthesis of an altered enzyme. The loss of AK activity in the Ado^r revertants suggests an association of the enhanced Ado sensitivity to the AK mutation.     

探讨医院图书馆数字化信息建设与服务

数字化信息时代,信息资源建设是主流的业务。本文通过对医院图书馆数字资源建设与知识服务的内容,提出医院图书馆信息资源数字化建设的基本对策和发展方向。     

The ecological footprint of dwelling construction in Spain

The construction industry is well known for its high impact on the environment; an even higher impact has taken place in recent years due to the real-estate bubble which has resulted in a surplus in the construction of dwellings in many countries. In Spain, about 500,000 dwellings were constructed during 2006–2010, which represent a 2% increase in four years. In the present work, a methodology is defined as the first step towards the creation of an effective assessment of the Ecological Footprint of this type of construction. The procedure is based on the project budget and its bill of quantities, organized by means of a systematic construction-work breakdown structure which divides the work into three major categories: materials, manpower, and machinery. Each stream generates partial footprints (i.e. energy, food, mobility, construction materials, and waste).Ninety-two dwelling construction projects, which represent the most commonly built dwellings in Spain per statistical data from the authorities, are evaluated and their ecological footprints are determined. The indicator is sensitive to various building typologies, which range from detached houses to multi-family buildings. Detached houses generate an ecological footprint per square metre constructed of 1.5 times higher than that of 4-floor multi-family buildings and the indicator remains practically constant for taller buildings. This emphasises that not only is the traditional Spanish construction of a compact city with multi-storey buildings environmentally better from the mobility standpoint, but also from the building construction standpoint.     

Abnormal locomotion in rats after bilateral intrastriatal injection of kainic acid.

The locomotion changes, after bilateral injection of kainic acid into the striata, are characterized by increased swing time and decreased stance time. This may be analogous to the locomotion pattern in patients with Huntington's Disease.     

Inhibition of photosynthetic oxygen evolution in non-vesicular preparations releases Mn2+ into a restricted aqueous compartment

Release of Mn2+ following inhibition of the water-splitting enzyme by treatment with Zn2+ was studied in two preparations derived from chloroplasts: oxygen-evolving Photosystem II membrane fragments and Tween-20 treated thylakoid membranes. In both cases the released Mn2+ was retained in the membrane fraction on centrifugation in spite of the fact that the two preparations are known to be non-vesicular. This suggests that upon inhibition Mn2+ is released into an aqueous compartment more restricted than the thylakoid lumen. We propose that this compartment is formed from the various proteins of the Photosystem II complex.     

K2[Zn(CV)2(H2O)2] · 2H2O: The first Zn(II) complex structurally characterized containing the pseudo-oxocarbon Croconate Violet (CV)

The synthesis, thermal behavior, spectroscopic characterization and crystal and molecular structure of a Zn(II) complex containing the pseudo-oxocarbon Croconate Violet (CV²⁻) dianion, namely K₂[Zn(CV)₂(H₂O)₂] · 2H₂O are reported. Thermal analysis has shown that the complex structure presents coordination and lattice water molecules. According to vibrational spectroscopy the Croconate Violet dianion is coordinated to Zn(II) center through the vicinal oxygen atoms in a chelating fashion with no involvement of CN moieties. The complex structure has been confirmed by single crystal X-ray diffraction analysis. The dianionic units [Zn(CV)₂(H₂O)₂]²⁻ adopt an slight distorted octahedral geometry in which the metallic center is surrounded by six oxygen atoms. These discrete dianionic units are connected through intermolecular hydrogen bonding giving rise to a supramolecular array extended along the crystallographic a axis.     

CT-guided 125I brachytherapy in the treatment of distant metastases in the oral cavity and maxillofacial region

PURPOSE: We aimed to evaluate the feasibility and clinical effectiveness of CT-guided ¹²⁵I brachytherapy for distant oral and maxillofacial metastases. MATERIALS AND METHODS: We retrospectively analyzed 65 patients with 84 distant oral and maxillofacial metastases. Thirty-one patients with 38 lesions received ¹²⁵I brachytherapy (group A) and 34 with 46 lesions received external beam radiotherapy (EBRT; group B). RESULTS: Median follow-up time was 16 months. The 3-, 6-, 12-, 18-, and 24-month local control rates for group A were 83.9%, 75.9%, 66.7%, 38.4%, and 25.0%, respectively; for group B they were 76.5%, 62.5%, 43.8%, 25.0%, and 0.0%, respectively (P < .05); the median local tumor progression-free survival times were 14 and 9 months, respectively. Group A had a better local tumor progression-free survival (LTPFS) relative to group B (P < .001; HR, 6.961 [95%CI, 2.109, 9.356]). Cox proportional hazards regression analysis indicated that ¹²⁵I brachytherapy, tumor size, and primary pathological type were the independent factors affecting LTPFS. Additionally, ¹²⁵I brachytherapy showed better performance in relieving patient clinical symptoms relative to EBRT (P < .05). Group A also had fewer complications than group B, especially regarding grade 3/4 complications according to Radiation Therapy Oncology Group grading criteria. Mean overall survival times in groups A and B were 17.1 and 14.8 months, respectively. CONCLUSION: CT-guided ¹²⁵I brachytherapy is feasible and safe for distant oral and maxillofacial metastases; it achieved a better local control rate, longer LTPFS and fewer complications without compromising overall survival compared with EBRT.     

Targeted α-Particle Radiation Therapy of HER1-Positive Disseminated Intraperitoneal Disease: An Investigation of the Human Anti-EGFR Monoclonal Antibody,Panitumumab

Identifying molecular targets and an appropriate targeting vehicle, i.e., monoclonal antibodies (mAb) and their various forms, for radioimmunotherapy (RIT) remains an active area of research. Panitumumab, a fully human and less immunogenic mAb that binds to the epidermal growth factor receptor (Erb1; HER1), was evaluated for targeted α-particle radiation therapy using ²¹²Pb, an in vivo α generator. A single dose of ²¹²Pb-panitumumab administered to athymic mice bearing LS-174T intraperitoneal (i.p.) tumor xenografts was found to have greater therapeutic efficacy when directly compared with ²¹²Pb-trastuzumab, which binds to HER2. A dose escalation study determined a maximum effective working dose of ²¹²Pb-panitumumab to be 20 μCi with a median survival of 35 days versus 25 days for the untreated controls. Pretreatment of tumor-bearing mice with paclitaxel and gemcitabine 24 hours prior to injection of ²¹²Pb-pantiumumab at 10 or 20 μCi resulted in the greatest enhanced therapeutic response at the higher dose with median survivals of 106 versus 192 days, respectively. The greatest therapeutic impact, however, was observed in the animals that were treated with topotecan 24 hours prior to RIT and then again 24 hours after RIT; the best response from this combination was also obtained with the lower 10-μCi dose of ²¹²Pb-panitumumab (median survival >280 days). In summary, ²¹²Pb-panitumumab is an excellent candidate for the treatment of HER1-positive disseminated i.p. disease. Furthermore, the potentiation of the therapeutic impact of ²¹²Pb-pantiumumab by chemotherapeutics confirms and validates the importance of developing a multimodal therapy regimen.