Central and peripheral changes in catecholamine-synthesizing enzyme activities after systemic administration of the neurotoxin DSP-4

In brain regions containing noradrenergic (NA) cell bodies or terminals, DSP-4 induces changes in the activity of catecholamine-synthesizing enzymes which suggest that central NA neurons are lesioned by this neurotoxin. In contrast, the lack of change in the same enzymatic activities in an area containing mostly adrenergic (A) neurons (C2 region), favors the hypothesis of a resistance of the A neurons to DSP-4. Furthermore, the enzymatic changes observed in peripheral organs suggest a peripheral activation of the NA cell bodies in response to lesioning of the sympathetic terminals by DSP-4.     

Self-administration in baboons and the discriminative stimulus effects in rats of bupropion,nomifensine, diclofensine and imipramine

The behavioral effects of the antidepressants nomifensine, diclofensine, bupropion, and imipramine were examined using a cocaine substitution drug self-administration procedure in baboons and a cocaine drug discrimination procedure in rats. Intravenous self-administration of the antidepressants was examined in baboons under conditions in which baseline responding was maintained by intravenous injections of cocaine HCl (0.32 mg/kg/injection). Drug was available under a fixed-ratio 80-response or 160-response schedule of intravenous injection. Each drug injection was followed by a 3-h time-out allowing a maximum of eight injections per day. The antidepressants or their vehicles were substituted for cocaine for a period of 15 days, followed by a return to the cocaine baseline. Nomifensine, diclofensine, and bupropion all maintained self-administration behavior at levels above those maintained by their respective vehicles. Some doses of nomifensine, diclofensine, and bupropion maintained levels of behavior similar to those maintained under baseline cocaine conditions. High doses of imipramine maintained levels of behavior above those maintained by its vehicle, but the amount of behavior maintained under these conditions was extremely small. In a second experiment rats were trained to discriminate 32 µmol/kg cocaine (IP 10 min presession) from no drug in a two-lever food reinforced drug discrimination procedure in which responding on one lever was reinforced following ten consecutive responses when the session was preceded by cocaine administration, while responding on the other lever was similarly reinforced in the absence of cocaine pretreatment. Cocaine, nomifensine, diclofensine, and bupropion all dose-dependently occasioned cocaine-appropriate responding. Imipramine did not occasion cocaine-appropriate responding over a range of behaviorally active doses.     

The antitumor effects of the quinoline-3-carboxamide linomide on Dunning R-3327 rat prostatic cancers.

Linomide (N-phenylmethyl-1,2-dihydro-4-hydroxyl-1-methyl-2-oxo-quinoline-3- carboxamide) is a quinoline 3-carboxamide which previously has been demonstrated to produce immunomodulator and antitumor effects when given in vivo. To test the possible antitumor effects of linomide against prostatic cancers, rats bearing five distinct Dunning R-3327 rat prostatic cancer sublines were treated daily with i.p. injections of linomide. These studies demonstrated that linomide has a reproducible antitumor effect against all of the prostatic cancers tested regardless of their growth rate, degree of morphologic differentiation, metastatic ability, or androgen responsiveness. This antitumor effect is observed only in vivo, not in vitro, and involves a cytotoxic response of the prostatic cancer cells. This cytotoxic response results in the retardation of the growth rate (i.e., increased tumor volume doubling time) of primary prostatic cancers and in metastatic lesions. Linomide's growth retardation is reversible, and thus continuous daily treatment with linomide is required for maximal antitumor response. Pretreatment of rats with linomide before tumor inoculation has no effect in addition to that produced by initiating linomide treatment at the time of tumor inoculation. No enhancement of either natural killer cell number or natural killer cell cytotoxic activity is induced by linomide treatment in the tumor-bearing rats. In addition, depletion of natural killer cell activity via injections of asialo-GM1 antiserum does not prevent the antitumor effects of linomide in vivo. Likewise, the antitumor effects of linomide are also produced in prostatic cancer-bearing athymic nude rats. These results suggest that the requirement for host involvement in the antitumor effects of linomide against rat prostatic cancers may involve both immune and nonimmune host mechanism(s) (e.g., antiangiogenesis).     

Salvage of ear cartilage in patients with acute full-thickness burns

Three cases in which the temporoparietal fascial flap was used to salvage denuded ear cartilage during the acute period after burn injury are reported. Patients' burns ranged from 30% to 75% total body surface area. The full-thickness burn was acutely excised, exposing the auricular cartilage. The temporoparietal facial flap was elevated and wrapped around the cartilage. The flap was then covered with a split-thickness skin graft. All flaps and skin grafts survived. Additional reconstructive procedures have been performed on two of the patients and are planned for the third.     

Standardization of factor IX: standards for "purified" factor IX concentrates.

An international collaborative study was carried out to determine the suitability of the current WHO II-IX-X concentrate standard, 84/681, for assigning potency to the more highly purified factor IX concentrates. Three Coagulation Factor IX (Human) preparations and one Factor IX Complex preparation were assayed by the one stage method against WHO 84/681 following predilution to 1.0 u/ml in buffer, 1% albumin, or factor IX deficient plasma. There were no cases of non-parallelism between any of the preparations and the current WHO standard. Predilution of the Coagulation Factor IX (Human) preparations in 1% albumin or factor IX deficient plasma gave similar potency values. Predilution in buffer gave significantly lower (p less than 0.01) potency values. For the Factor IX Complex preparation, potency estimates were significantly different (p less than 0.01) with each prediluent. The overall precision was similar within each predilution for all preparations with predilution in buffer being less precise than predilution in albumin or in deficient plasma. WHO standard 84/681 appears to be a suitable standard for the potency determination of the more highly purified factor IX preparations. Predilution in 1% albumin or factor IX deficient plasma is recommended as they give equivalent results with the least variability.     

Localisation of a pulmonary autoantigen in cryptogenic fibrosing alveolitis.

BACKGROUND--Cryptogenic fibrosing alveolitis (CFA) is believed to have an immunological pathogenesis with a persisting inflammatory reaction to an as yet unidentified pulmonary antigen(s). A high frequency of IgG autoantibodies has previously been found in the plasma of patients with CFA to an extractable 70-90 kDa lung antigen by Western blotting. Preliminary immunohistochemical studies with patient IgG had indicated that the target protein(s) might be associated with alveolar epithelial lining cells which have previously been suggested as the site of immunological attack in CFA. METHODS--In order to confirm this finding immunohistochemical analysis and Western blotting were performed on a human type II alveolar cell line (A549) using CFA patient plasma. In order to study further the distribution of the antigen, antibodies were raised in a rabbit to the partially purified 70-90 kDa CFA lung protein. RESULTS--The results showed that the human CFA autoantibody recognised a 70-90 kDa protein with a cytoplasmic distribution present in the A549 cells, confirming previous observations. The immune rabbit IgG recognised a protein of similar molecular weight by Western blotting of protein derived from lung biopsy samples of patients with CFA and A549 cells. In addition it immunoprecipitated protein(s) of this molecular weight from lung biopsy protein extracts from patients with CFA. The precipitated protein(s) were found to cross-react with the autoantibody found in the plasma of patients with CFA. Immunohistochemical analysis with immunised rabbit antibody revealed positive staining of type I and II alveolar epithelial lining cells in CFA. A similar pattern of epithelial staining was also observed with the rabbit IgG on biopsy specimens of lung from patients with sarcoidosis and control lung tissue, although this was more focal and less intense. No positive staining was seen on sections from a number of non-pulmonary tissues (colon, liver, kidney, tonsil, lymph node, skin, cervix). Cytoplasmic staining of the A549 cell line was also detected. CONCLUSIONS--The 70-90 kDa protein recognised by autoantibodies in patients with CFA is associated with pulmonary epithelial lining cells. The immune rabbit IgG produced appears to recognise antigen by Western blotting and immunohistochemical staining of lung tissue in a similar pattern to the patient autoantibodies. Immunohistochemical data obtained with this antibody suggest that the putative autoantigen against which patients with CFA mount a humoral immune response may be endogenous and specific to the lung.     

Total anomalous pulmonary venous drainage. Seventeen-year surgical experience

Between 1968 and 1985, 80 children underwent correction of total anomalous pulmonary venous drainage. There were 47 boys and 33 girls whose ages ranged from 3 days to 16 years (median 2 months, interquartile range 5 years). Seventy (87.5%) were less than 1 year of age at operation. Fifty-eight (72.5%) weighed less than 5 kg, the range being 1.6 to 42 kg (median 3.7 kg, interquartile range 2.4 kg). Forty-five (56%) patients had supracardiac, 14 (17.5%) cardiac, 15 (19%) infracardiac, and 6 (7.5%) had mixed total anomalous pulmonary venous drainage. Follow-up was complete in 78 (97.5%) and ranged from 6 to 189 months (median 58 months, interquartile range 59 months). There were 14 (17.5%) early and six (7.5%) late deaths. Analysis by various factors revealed year of operation as the only factor to affect survival at the 5% level of significance. Early mortality was 29% between 1968-1977 and 11% between 1978-1985 (p = 0.04). Postoperative pulmonary venous obstruction occurred in five (6%) patients between 6 weeks and 3 months after operation. All 5 died, three after reoperation. Five (6%) other children had reoperations, four for residual shunts and one for superior vena caval obstruction.     

Assessment of global and regional left ventricular function and volumes with 64-slice MSCT: a comparison with 2D echocardiography.

BACKGROUND: In patients with coronary artery disease (CAD), LV function and volumes are important parameters for long-term prognosis. Multislice computed tomography (MSCT) allows noninvasive assessment of the coronary arteries, but the accuracy of 64-slice MSCT for the assessment of left ventricular (LV) volumes and function is unknown. METHODS AND RESULTS: A head-to-head comparison between 64-slice MSCT and 2-dimensional (2D) echocardiography was performed in 40 patients with known or suspected CAD. The LV end-diastolic volume (LVEDV) and LV end-systolic volume (LVESV) were determined and the LV ejection fraction (LVEF) was derived. Regional wall motion was assessed visually using a 17-segment model. A 3-point scoring system was used to assign to each segment a wall motion score: 1 = normokinesia, 2 = hypokinesia, 3 = akinesia or dyskinesia. Two-dimensional echocardiography served as the gold standard. MSCT agreed well with 2D echocardiography for assessment of LVEDV (r = 0.97; p < .0001) and LVESV (r = 0.98; p < .0001). An excellent correlation between MSCT and 2D echocardiography was shown for the evaluation of LVEF (r = 0.91; p < .0001). Agreement for the assessment of regional wall motion was excellent (96%, kappa = 0.82). CONCLUSIONS: An accurate assessment of global and regional LV function and volumes is feasible with 64-slice MSCT.     

3,5-甾二烯化合物的合成及抗早孕活性

以18-甲基-17β-羟基-17α-乙炔基-雌甾-4-烯-3-酮(18-甲基炔诺酮),17β-羟基-17α-乙缺基-雌甾-4-烯-3-酮(炔诺酮),17β-羟基-17α-乙炔基-雄甾-4-烯-3-酮(妊娠素)和17a-羟基孕甾-4-烯-3,20二酮(17α-羟基黄体酮)为原料,经NaBH,还原、脱水、双键转位和酯化等反应合成一系列3,5-甾二烯化合物,用¹HNMR和MS证明了它们的结构。动物筛选结果表明,17β-丙酰氧基-17α-乙炔基-雌甾-3,5-二烯(IV_b2有明显的抗早孕活性。中断早期妊娠的作用似与其雌激素活性有关。