蝙蝠葛中的新生物碱——蝙蝠葛新林碱

防已科植物蝙蝠葛(Menispermum daurioum DC.)的根茎,即北豆根,是一种重要的中药,具有清热解毒、消肿止痛等功效。已知含有近二十种生物碱,其中五种属双苄基四氢异喹啉类,即蝙蝠葛碱(dauricine,Ⅰ)、蝙蝠葛诺林碱(daurinoline,Ⅱ)、蝙蝠葛新诺林碱     

Immune responses against SARS-coronavirus nucleocapsid protein induced by DNA vaccine

The nucleocapsid （N） protein of SARS-coronavirus （SARS-CoV） is the key protein for the formation of the helical nucleocapsid during virion assembly. This protein is believed to be more conserved than other proteins of the virus, such as spike and membrane glycoprotein. In this study, the N protein of SARS-CoV was expressed in Escherichia coli DHSalpha and identified with pooled sera from patients in the convalescence phase of SARS. A plasmid pCI-N, encoding the full-length N gene of SARS-CoV, was constructed. Expression of the N protein was observed in COS1 cells following transfection with pCI-N. The immune responses induced by intramuscular immunization with pCI-N were evaluated in a murine model. Serum anti-N immunoglobutins and splenocytes proliferative responses against N protein were observed in immunized BALB/c mice. The major immunoglobulin G subclass recognizing N protein was immunoglobulin G2a, and stimulated splenocytes secreted high levels of gamma interferon and IL-2 in response to N protein. More importantly, the immunized mice produced strong delayed-type hypersensitivity （DTH） and CD^8＋ CTL responses to N protein.     

Microtubule reassembly in surface-activated platelets

It is generally accepted that a circumferential microtubule supports the discoid shape of resting platelets. The fate of the many-coiled polymer following platelet activation, however, has been a subject of considerable debate. Morphological investigations have suggested that the circumferential coils are constricted into tight rings around centrally concentrated organelles during platelet shape change. Biochemical studies employing colchicine-binding assays, on the other hand, have indicated that the bundle of microtubules dissolves almost completely within seconds after activation and reassembles in a new location one to four minutes later. The present study has accepted the latter hypothesis in order to examine the second part of the disassembly-reassembly theory proposed in biochemical studies. Platelets exposed to low temperatures sufficient to remove all microtubules were placed on glass slides and microscope grids to cause surface activation during rewarming. The combined stimuli of rewarming and surface activation might have been expected to cause more rapid assembly than warming alone or activation alone. This was not the case. Reassembly of microtubules during rewarming and simultaneous surface activation was not accelerated. In contrast to the constriction of microtubule rings observed during activation in control platelets, the diameters of coils that developed in chilled platelets one to two hours after rewarming and surface activation were twice those of control cells.     

Curative potential of multimodality therapy for locally recurrent rectal cancer

OBJECTIVE: To assess the results of multimodality therapy for patients with recurrent rectal cancer and to analyze factors predictive of curative resection and prognostic for overall survival. SUMMARY BACKGROUND DATA: Locally recurrent rectal cancer is a difficult clinical problem, and radical treatment options with curative intent are not generally accepted. METHODS: A total of 394 patients underwent surgical exploration for recurrent rectal cancer. Ninety were found to have unresectable local or extrapelvic disease and 304 underwent resection of the recurrence. The latter patients were prospectively followed to determine long-term survival and factors influencing survival. RESULTS: Overall 5-year survival was 25%. Curative, negative resection margins were obtained in 45% of patients; in these patients a 5-year survival of 37% was achieved, compared to 16% (P <.001) in patients with either microscopic or gross residual disease. In a logistic regression analysis, initial surgery with end-colostomy and symptomatic pain (both univariate) and increasing number of sites of the recurrent tumor fixation in the pelvis (multivariate) were associated with palliative surgery. Overall survival was significantly decreased for symptomatic pain (P <.001) and more than one fixation (P =.029). Survival following extended resection of adjacent organs was not different from limited resection (28% vs. 21%, P =.11). Patient demographics and factors related to the initial rectal cancer did not affect outcome. Perioperative mortality was only 0.3%, but significant morbidity occurred in 26% of patients, with pelvic abscess being the most common complication. CONCLUSIONS: This study demonstrates that many patients with locally recurrent rectal cancer can be resected with negative margins. Long-term survival can be achieved, especially for patients with no symptoms and minimal fixation of the recurrence in the pelvis, provided no gross residual disease remains.     

The normal development of tibial torsion

Objective: Pathological rotation of the leg is a well-known problem in paediatric orthopaedics. In this study the normal development of tibial torsion during growth was evaluated by computed tomography (CT). Design: Seventy-eight normal individuals (52 children, 26 adults) aged 3–51 years were examined with CT. In axial scans the angle between a line tangential to the posterior part of the femoral condyles and the intermalleolar line, a line through the centre of the lateral and medial malleolus, was measured. The radiation exposure was evaluated and accepted by The National Department for Radiation and the Regional Committee for Ethics in Science. Results: CT showed that the average lateral torsion of the leg at the age of 4 years was 28° with an individual variation of 20°–37°. Later the increase in tibial torsion was on average 1°/year until 10 years of age and, thereafter, 4° until maturity when the mean lateral torsion was 38° (18°–47°). Conclusion: Tibial torsion in children mainly develops during the first 4 years of life. After this the increase was of less clinical significance. Received: 13 November 2000 Revision requested: 26 February 2001 Revision received: 19 March 2001 Accepted: 18 April 2001     

Duration of Lactation and Incidence of the Metabolic Syndrome in Women of Reproductive Age According to Gestational Diabetes Mellitus Status: A 20-Year Prospective Study in CARDIA (Coronary Artery Risk Development in Young Adults)

OBJECTIVE

The objective of the study was to prospectively assess the association between lactation duration and incidence of the metabolic syndrome among women of reproductive age.

RESEARCH DESIGN AND METHODS

Participants were 1,399 women (39% black, aged 18–30 years) in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, an ongoing multicenter, population-based, prospective observational cohort study conducted in the U.S. Women were nulliparous and free of the metabolic syndrome at baseline (1985–1986) and before subsequent pregnancies, and reexamined 7, 10, 15, and/or 20 years after baseline. Incident metabolic syndrome case participants were identified according to National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. Complementary log-log models estimated relative hazards of incident metabolic syndrome among time-dependent lactation duration categories by gestational diabetes mellitus (GDM) adjusted for age, race, study center, baseline covariates (BMI, metabolic syndrome components, education, smoking, physical activity), and time-dependent parity.

RESULTS

Among 704 parous women (620 non-GDM, 84 GDM), there were 120 incident metabolic syndrome case participants in 9,993 person-years (overall incidence rate 12.0 per 1,000 person-years; 10.8 for non-GDM, 22.1 for GDM). Increased lactation duration was associated with lower crude metabolic syndrome incidence rates from 0–1 month through >9 months (P < 0.001). Fully adjusted relative hazards showed that risk reductions associated with longer lactation were stronger among GDM (relative hazard range 0.14–0.56; P = 0.03) than non-GDM groups (relative hazard range 0.44–0.61; P = 0.03).

CONCLUSIONS

Longer duration of lactation was associated with lower incidence of the metabolic syndrome years after weaning among women with a history of GDM and without GDM, controlling for preconception measurements, BMI, and sociodemographic and lifestyle traits. Lactation may have persistent favorable effects on women''s cardiometabolic health.Lactation has favorable effects on cardiometabolic risk factors in women with and without a history of gestational diabetes mellitus (GDM), a strong predictor of type 2 diabetes (1,2) and the metabolic syndrome after pregnancy (3). In the general population, lactating compared with nonlactating women exhibit a less atherogenic lipid profile (4) and lower blood glucose and insulin concentrations (5). Consistent with these findings, lactating women with recent GDM experience lower fasting plasma glucose and insulin levels, higher plasma HDL cholesterol levels, and 50% lower prevalence of type 2 diabetes at 12–16 weeks postpartum (6,7).Yet, few studies have investigated whether lactation''s favorable effects on cardiometabolic risk factors persist after weaning to protect women against future disease. The only study, to our knowledge, to measure changes from preconception to after weaning reported 6-mg/dl higher average HDL cholesterol levels among women who lactated for ≥3 months versus <3 months independent of preconception plasma HDL cholesterol levels and weight gain (8). Epidemiologic studies have reported weak to modest protective associations between lactation and disease risk in midlife to late life, including lower prevalence of the metabolic syndrome (9,10) or cardiovascular risk factors (11) and lower incidence of myocardial infarction (12) and type 2 diabetes (13). Yet, evidence is lacking that directly links risk factor changes that persist after weaning to subsequent disease onset, because disease status and lactation history were ascertained decades after pregnancy, and preconception and/or postweaning risk factor measurements were not available (9–13). Other limitations include classification of outcomes via self-report only (11–13), and failure to account for mediating or confounding effects of lifestyle habits during the reproductive years. Lastly, lactation duration in relation to disease risk has not been examined separately among women with a history of GDM, with the exception of one study reporting a null association with incident diabetes (13).To our knowledge, studies have never examined lactation and incidence of the metabolic syndrome, or variation in disease risk by GDM status. To address these gaps, we prospectively examined whether increasing duration of lactation was associated with lower incidence of the metabolic syndrome during a 20-year period among women of childbearing age. We examined incidence rates for GDM and non-GDM pregnancies and controlled for preconception risk factor levels, sociodemographics, and follow-up behavioral attributes.