Nidovirus infections: experimental model systems of human neurologic diseases

The presence of terminally differentiated slow- and non-dividing cells in the central nervous system (CNS) provides a safe harbor for viral persistence and latency and constitutes a unique immunologic environment for viral infections. Studies of experimental model systems of viral infections of the CNS provide insight into mechanisms of viral persistence and immune-mediated pathology. Nidoviruses are comprised of 2 families of viruses, coronaviruses and arteriviruses, and are common pathogens of humans and a variety of animal species. Both families of viruses contain neurotropic strains that produce experimental neurologic diseases in rodents. These include acute meningitis and encephalitis; acute poliomyelitis; and chronic inflammatory, immune-mediated, demyelination. Coronavirus-induced demyelinating disease mimics many of the pathologic features of Multiple Sclerosis (MS).     

Laboratory monitoring of pentasaccharide in a dog model of hemodialysis

Varying dosages of pentasaccharide (400-800 nmol/kg) were compared to a 250-U/kg single bolus dosage of unfractionated heparin (UFH) in a dog model of hemodialysis. Several laboratory assays were used to monitor the effects of pentasaccharide and UFH. The pentasaccharide did not produce any anticoagulant effects as measured by the activated partial thromboplastin time. However, in the anti-Xa chromogenic assay and the Heptest assays, there was a dose-dependent prolongation after pentasaccharide administration. In the group of dogs administered 800 nmol/kg of pentasaccharide, there was a 50% decrease in the thrombin antithrombin (TAT) complex level after 60 minutes on dialysis. In the UFH-treated dogs, wide variations in assays were observed. There was a marked elevation in the activated partial thromboplastin time and Heptest assays up to 6 hours after UFH administration. Both anti-Xa and anti-IIa activity was measured up to 4 hours. In the TAT assay, UFH was found to have a stronger effect in suppressing the formation of TAT in comparison to the pentasaccharide. These results suggest that pentasaccharide can be used as a replacement for UFH in a dog model of hemodialysis to keep the dialysis circuit patent. In addition, the anti-Xa-based assays such as the Heptest and the chromogenic anti-Xa assays can be used to monitor the effects of pentasaccharide in this model.     

Simple, Rapid Enzyme-Linked Immunosorbent Assay (ELISA) for the Determination of Rat Osteocalcin

Determination of the concentration of osteocalcin in rat serum is frequently performed using a commercially available radioimmunoassay (RIA). However, this assay takes 3 days to complete, uses radioactive material, and has a narrow linear range. The limited range of the RIA makes it necessary to test multiple dilutions of the sample which frequently results in values that differ, depending on the dilution. In order to overcome these limitations, we have developed an ELISA that utilizes the same standards and anti-rat osteocalcin antiserum, as is used in the RIA. The principle of the ELISA is that the osteocalcin in the sample competes with osteocalcin previously immobilized on a microtiter plate to bind to the available anti-rat osteocalcin antibodies. The amount of antibody bound to the immobilized osteocalcin is determined colorimetrically using a secondary antibody coupled to alkaline phosphatase. This ELISA has a three-log linear response with a sensitivity of 0.1–0.15 ng/ml and intra- and interassay coefficient of variance (CV) values of less than 10%. Most importantly, the assay is rapid and only requires a 2-hour incubation of the sample with the antiserum. The incubation time is important since we and others have observed a significant decrease in the osteocalcin level from serum samples incubated for long periods of time with the antiserum, presumably due to degradation of the osteocalcin. In general, the commercially available RIA gives osteocalcin values that are one-half to one-fourth that of the ELISA because the RIA requires a 48-hour incubation time. Received: 14 November 1997 / Accepted: 9 July 1998     

Paget病19例

目的 提高对Ｐａｇｅｔ病的诊治水平。方法 回顾性分析１９８７年至１９９７年收治的１９例Ｐａｇｅｔ病的临床表现及诊治方法。结果 本组乳腺Ｐａｇｅｔ病６例,乳腺外１３例,其中阴茎,阴囊１１例,腹股沟处１例,肛周肛管１例。随访时间０．５－１１年,平均５年４个月,随访中３例复发者,其截端切片病理检查均可见病变组织,另１例死于其他疾病。     

Characterization of melanocortin receptor ligands on cloned brain melanocortin receptors and on grooming behavior in the rat.

Since the melanocortin MC3 and melanocortin MC4 receptors are the main melanocortin receptor subtypes expressed in rat brain, we characterized the activity and affinity of nine melanocortin receptor ligands using these receptors in vitro, as well as their activity in a well-defined melanocortin-induced behavior in the rat: grooming behavior. We report here that [D-Tyr4]melanotan-II and RMI-2001 (Ac-cyclo-[Cys4, Gly5, D-Phe7, Cys10]alpha-MSH-NH2) have significantly higher affinity and potency on the rat melanocortin MC4 receptor as compared to the rat melanocortin MC3 receptor. Nle-gamma-MSH (melanocyte-stimulating hormone) was the only ligand with higher affinity and potency on the rat melanocortin MC3 receptor. The potency order of melanocortin MC4 receptor agonists, but not that of melanocortin MC3 receptor agonists, fitted with the potency of these ligands to stimulate grooming behavior, when administered intracerebroventricularly. SHU9119 (Ac-cyclo-[Nle4, Asp5, D-Nal(2)7, Lys10]alpha-MSH-(4-10)-NH2) and RMI-2005 (Ac-cyclo-[Cys4, Gly5, D-Na](2)7, Nal(2)9, Cys10]alpha-MSH-(4-10)-NH2) were able to inhibit alpha-MSH-induced melanocortin receptor activity in vitro, as well as alpha-MSH-induced grooming behavior. Melanotan-II, [Nle4-D-Phe7]alpha-MSH and RMI-2001 were also effective in inducing grooming behavior when administered intravenously. In the absence of purely selective melanocortin MC(3/4) receptor ligands, we demonstrated that careful comparison of ligand potencies in vitro with ligand potencies in vivo, could identify which melanocortin receptor subtype mediated alpha-MSH-induced grooming behavior. Furthermore, blockade of novelty-induced grooming behavior by SHU9119 demonstrated that this physiological stress response is mediated via activation of the melanocortin system.     

1-N HAPA gentamicin B, a new aminoglycoside active against gentamicin resistant isolates--activity compared to other aminoglycosides.

1-N HAPA gentamicin B is a new aminoglycoside active against most Enterobacteriaceae, Pseudomonas aeruginosa and Staphylococcus aureus. Among 504 clinical isolates at a concentration of 12.5 microgram/ml all Staph. aureus, Escherichia coli, Klebsiella, Enterobacter, Proteus rettgeri, Providencia and 78% of Pseudomonas, 86% of Proteus morganii were inhibited. Like other aminoglycosides, the activity was greatest at an alkaline ph and reduced by high cations concentrations. 1-N HAPA gentamicin B was equal in activity to amikacin against both gentamicin-sensitive and resistant isolates. It inhibited bacteria containing many of the aminoglycoside inactivating enzymes. When combined with carbenicillin it inhibited in a synergistic manner many Gram-negative bacteria, particularly Pseudomonas and Serratia.     

Cyclopenta-polycyclic aromatic hydrocarbons: potential carcinogens and mutagens

Cyclopenta-polycyclic aromatic hydrocarbons (cyclopenta-PAHs) are a group of compounds that have been detected as environmental pollutants. Perturbation molecular orbital (PMO) calculations on their presumed ultimate carcinogenic metabolites, the cyclopenta-PAH expoxides, predict that they may have a greater biological hazard than the classic PAHs.     

母鸡在排卵周期和抱窝血浆“黄体生成素类似物”和孕酮的浓度变化

本文用放射免疫分析法(RTA)测定了泰和母鸡在排卵周期和抱窝的不同生殖阶段,血浆“黄体生成素类似物”(“LH”)和孕酮(P)的浓度。结果表明:母鸡在排卵周期血浆“LH”和P的平均值分别为3.67±0.60ng/ml(x±SE)和459.50±30.87pg/ml,排卵前6～3h,血浆“LH”和P均出现浓度高峰,其峰值比相应的平均值高出1.1和1.3倍,差异非常显著(P<0.01)。抱窝鸡血浆“LH”和P在24h内的平均值分别为2.27±0.22ng/ml和319.46±12.15pg/ml,显著地低于母鸡在排卵周期的平均值(P<0.05),且在24h内的不同时间,未见有浓度高峰出现。     

Dynamic study on superficial blood flow in patients with acute myocardial infarction]

Fourteen points superficial bloodflow (SBF) of the skin and tongue in 55 patients with acute myocardial infarction (AMI) were measured at 12, 24, 36, 48, 60 hours and 3, 5, 7, 10, 14, 21, 28 days after AMI by LDF (PF2). The dynamic study on multiple points SBF of 576 times showed that (1) The mean SBF of skin was 1.0 +/- 0.04 (V) at 12 hours after AMI. It occupied 70.5% in the normal control. After therapy at 48 hours of AMI, the mean SBF was increased to 1.20 +/- 0.03 (V), and approximated 85.9% of the control. (2) The mean SBF in patients with cardiogenic shock was 1.04 +/- 0.05 (V), and it was significantly lower than that without complications (P less than 0.01). The mean SBF showed a negative correlation with the nailfold microcirculatory values (P less than 0.0025). There was a negative correlation between "Tanzhong" SBF and cardiac muscle enzyme CPK, GOT, LDH (P less than 0.05). (3) The SBF of acupuncture point "Tanzhong, Erxin" related to the heart might more sensitively represent the cardiac condition in AMI. (4) The SBF of tongue was negatively correlated with GOT (P less than 0.05). (5) Continual peripheral microcirculatory observation and electrocardiographic monitoring would be helpful in the diagnosis and treatment of earlier complications of AMI in order to reduce the mortality.