Presence of lysine at aa 335 of the hemagglutinin-neuraminidase protein of mumps virus vaccine strain Urabe AM9 is not a requirement for neurovirulence

The recent global resurgence of mumps has drawn attention to the continued need for robust mumps immunization programs. Unfortunately, some vaccines derived from inadequately attenuated vaccine strains of mumps virus have caused meningitis in vaccinees, leading to withdrawal of certain vaccine strains from the market, public resistance to vaccination, or in some cases, cessation of national mumps vaccination programs. The most widely implicated mumps vaccine in cases of postvaccination meningitis is derived from the Urabe AM9 strain, which remains in use in some countries. The Urabe AM9 vaccine virus has been shown to exhibit a considerable degree of nucleotide and amino acid heterogeneity. Some studies have specifically implicated variants containing a lysine residue at amino acid position 335 in the hemagglutinin-neuraminidase (HN) protein with neurotoxicity, whereas a glutamic acid residue at this position was associated with attenuation. To test this hypothesis we generated two modified Urabe AM9 cDNA clones coding either for a lysine or a glutamic acid at position 335 in the HN gene. The two viruses were rescued by reverse genetics and characterized in vitro and in vivo. Both viruses exhibited similar growth kinetics in neuronal and non-neuronal cell lines and were of similar neurotoxicity when tested in rats, suggesting that amino acid 335 is not a crucial determinant of Urabe AM9 growth or neurovirulence.     

COPD机械通气病人下呼吸道感染致病菌分布特点

①目的 探讨慢性阻塞性肺病(COPD)病人机械通气后下呼吸道感染致病菌的特点。②方法 取32例COPD并发呼吸衰竭行机械通气病人下呼吸道分泌物做痰细菌学培养，同时做药物敏感试验。③结果 32例病人共分离出菌株76株，阳性率71．7％，其中混合感染10例次。其中革兰阴性杆菌(GNB)58株，占76．3％；阳性球菌10株，占13．2％；真菌8株，占10．5％。常见致病菌以铜绿假单胞菌、鲍曼不动杆菌和肺炎杆菌为主，GNB中铜绿假单胞菌和不动杆菌的耐药率高。④结论 COPD应用机械通气病人下呼吸道感染以革兰阴性杆菌为主，耐药性高。     

Obesity: determinants and therapeutic initiatives.

There are several possible determinants of obesity, including impaired thermogenesis and the differential utilization of fuels in different tissues. Whereas hypometabolism may initiate obesity in some people, once obese, individuals tend to manifest a higher resting metabolic rate because of their greater fat-free mass, exhibit an impaired thermic response to food, and expend more calories than lean individuals for equivalent amounts of activity. As a result, over a 24-h period, obese people generally expend more energy than lean people. A second determinant of obesity is related to fuel utilization and suggests that those predisposed to be obese may have an innate insulin resistance in muscle, leading to decreased uptake, oxidation, and storage of glucose in this tissue. As a result, the glucose is shunted to adipose tissue, where it is stored. With regard to treatment of obesity, emphasis on increased energy expenditure through the inclusion of reasonable amounts of activity is essential. However, this must always be combined with restraint in caloric intake.     

Revascularization of the renal artery in renovascular hypertension with progressive renal insufficiency

Sixteen patients underwent surgical treatment for severe renovascular hypertension with rapidly progressive renal failure. These patients were assessed preoperatively with the measurement of serum creatinine and blood-urea levels (means 271 +/- 204 mumol/l and 15.6 +/- 10.3 mmol/l respectively), and renal clearances. 5 patients underwent aorto-renal bypass (bilateral in one case) and 11 patients were treated by autotransplantation of the kidney. Operative mortality was 6.2%. Early results were assessed at 1 and 6 months postoperatively. Renal function was normal in 8 patients, improved in 5 (p less than 0.05), unchanged in 1 and worse in 1 by aorto-renal bypass thrombosis. At long-term with a minimum follow-up of 12 months (mean 31 +/- 12 months), the initial improvement in renal function remained steady in 12 patients whilst 1 patient has gone on to hemodialysis. At middle and long-term, 81% of the patients were normotensive without medication or had improved blood pressure (p less than 0.001). These good results confirm the reversibility of renal ischemic lesions and support an aggressive attitude towards the use of revascularization in the surgical treatment of such patients with renovascular hypertension and renal failure.     

Brain natriuretic peptide enhances the endothelium-independent cAMP and vasorelaxant responses of calcitonin gene-related peptide in rat aorta

Calcitonin gene-related peptide (CGRP) causes vasorelaxation in rat aorta involving endothelium/nitric oxide (NO)-dependent elevations of both cAMP and cGMP levels. When endothelium is removed, preincubation with exogenous NO uncovers and potentiates direct (endothelium-independent) cAMP elevations and vasorelaxations caused by CGRP. This enhancing effect of NO potentially involves elevation of cGMP and inhibition of Type III (cGMPinhibitable) phosphodiesterase, causing accumulation of cAMP. However, NO may have other actions. The aim of the present study was to determine if brain natriuretic peptide (BNP), which elevates cGMP levels independent of NO, could enhance cAMP accumulations and vasorelaxations induced by CGRP in rat aortic rings denuded of endothelium. When added separately, neither CGRP (100 nM) nor BNP (10 nM) altered cAMP levels. When added in combination, CGRP (100 nM) and BNP (10 nM) significantly elevated cAMP levels (from control of 0.95 ± 0.08 to 1.53 ± 0.09 pmol/mg protein) at 2 min. BNP (10 nM) elevated cGMP levels 10-fold at 2 min and this response was not altered by co-administration of CGRP (100 nM).Pretreatment with BNP at concentrations as low as 1 nM in endothelium-denuded aortic rings greatly enhanced the direct vasorelaxant effects of CGRP (100 nM) (from control of 0% to 57.6 ± 6.8% relaxation of phenylephrineprecontractions). Our findings indicate that BNP enhances direct (endothelium-independent) cAMP elevations and vasorelaxations caused by CGRP in rat aorta, thus supporting the concept that cGMP inhibits cAMP metabolism and enhances CGRP-induced responses in aortic smooth muscle cells.     

Reizhusten, Belastungsdyspnoe und zystische Lungenveränderungen bei einem 28jährigen Patienten

Zusammenfassung Eine neu aufgetretene Dyspnoesymptomatik und eine symmetrische, apikal betonte retikulonodul?re Zeichnungsvermehrung im R?ntgen-Thorax bei jungen rauchenden Erwachsenen müssen an das seltene Krankheitsbild der pulmonalen Histiocytosis X denken lassen. Klinischer Befund, laborchemische- und Lungenfunktionsuntersuchungen zeigen unspezifische Befunde. Neue radiologische Verfahren wie die hochaufl?sende Computertomographie (HRCT) leisten bei gezielter Indikationsstellung eine entscheidende differentialdiagnostische Hilfestellung. Dieser Fall verdeutlicht die M?glichkeit einer Diagnosesicherung durch transbronchiale Biopsien unter Verzicht auf offene Lungenbiopsien. Eine ambulante Diagnostik war m?glich, das h?here Risiko eines operativen Eingriffes konnte vermieden werden. Die Indikation zur Therapie ist nicht gesichert und wird daher durch den Grad der subjektiven bzw. funktionellen Einschr?nkung sowie den Verlauf bestimmt.     

A preliminary study of the changes in the direct-acting mutagenicities of several nitropolycyclic aromatic hydrocarbons after exposure under sunlight

Five commercially available nitropolyclyclic aromatic hydrocarbons (nitro-PAH), namely, 4-nitrobiphenyl, 2-nitrofluorene, 9-nitroanthracene, 1-nitropyrene, and 2,7-dinitrofluorene, were exposed under restricted sunlight in the open air. The direct-acting mutagenicities of the samples after an exposure of 45 days were measured in order to compare them with those of the original samples in the Ames Salmonella typhimurium bioassay. It was found that the mutagenicities of some nitro-PAH do not change significantly while the mutagenicities of others increase or decrease after exposure. A preliminary study of nitro-PAH reaction products after exposure using GC, GC/MS, and FT-IR is also reported.