Protective immunity to infectious bronchitis in broilers vaccinated against Marek's disease either in ovo or at hatch and against infectious bronchitis at hatch.

Two experiments were conducted using commercial broiler chickens to determine if Marek's disease (MD) vaccines HVT/SB-1 and HVT plus CVI-988 given either in ovo or at hatch adversely affected the efficacy of infectious bronchitis (IB) vaccines (Ark and Mass serotypes) given by eyedrop on the day of hatch. Nonvaccinated negative controls and controls that received only IB vaccines were included in each study. Birds were challenged with either infectious bronchitis virus (IBV) Mass-41 or IBV Ark-99 on either day 26 or 27 of age. Protection was assessed 5 days post-IBV challenged by virus isolation from the trachea. The day of hatch mean antibody titer to IBV was 12,668 +/- 4704 and 2503 +/- 3243 by enzyme-linked immunosorbent assay in experiments 1 and 2, respectively. In each study, nonvaccinated controls had a significantly higher (P < or = 0.05) incidence (88%-100%) of IBV challenge virus isolation than did controls vaccinated for IB but not for MD. Analysis of data from both studies showed that protection to IB in groups that received only IB vaccines at hatch ranged from 55.0% to 77.3%, whereas protection to IB in groups receiving both MD and IB vaccines ranged from 50.0% to 95.5%. In both experiments and within IBV challenge serotype, broilers given MD vaccines (in ovo or at hatch) and IB vaccines at hatch had protection rates to IBV challenges that were not significantly less (P < or = 0.05) than IB protection rates of groups that received only IB vaccines at hatch. Analysis of these data shows that administration of high-titered MD vaccines either in ovo or at hatch did not affect the efficacy of an IB vaccination (serotypes Ark and Mass) given by eyedrop at hatch.

Refined 2.3 A X-ray crystal structure of bovine thrombin complexes formed with the benzamidine and arginine-based thrombin inhibitors NAPAP, 4-TAPAP and MQPA. A starting point for improving antithrombotics.

Well-diffracting crystals of bovine epsilon-thrombin in complex with several "non-peptidic" benzamidine and arginine-based thrombin inhibitors have been obtained by co-crystallization. The 2.3 A crystal structures of three complexes formed either with NAPAP, 4-TAPAP, or MQPA, were solved by Patterson search methods and refined to crystallographic R-values of 0.167 to 0.178. The active-site environment of thrombin is only slightly affected by binding of the different inhibitors; in particular, the exposed "60-insertion loop" essentially maintains its typical projecting structure. The D-stereoisomer of NAPAP and the L-stereoisomer of MQPA bind to thrombin with very similar conformations, as previously inferred from their binding to bovine trypsin; the arginine side-chain of the latter inserts into the specificity pocket in a "non-canonical" manner. The L-stereoisomer of 4-TAPAP, whose binding geometry towards trypsin was only poorly defined, is bound to the thrombin active-site in a compact conformation. In contrast to NAPAP, the distal p-amidino/guanidino groups of 4-TAPAP and MQPA do not interact with the carboxylate group of Asp189 in the thrombin specificity pocket in a "symmetrical" twin N-twin O manner, but through "lateral" single N-twin O contacts; in contrast to the p-amidino group of 4-TAPAP, however, the guanidyl group of MQPA packs favourably in the pocket due to an elaborate hydrogen bond network, which includes two entrapped water molecules. These thrombin structures confirm previous conclusions of the important role of the intermolecular hydrogen bonds formed with Gly216, and of the good sterical fit of the terminal bulky hydrophobic inhibitor groups with the hydrophobic aryl binding site and the S2-cavity, respectively, for tight thrombin active site binding of these non-peptidic inhibitors. These accurate crystal structures are presumed to be excellent starting points for the design and the elaboration of improved antithrombotics.

Episodic and semantic memory in early versus late onset Alzheimer's disease.

The aim of this study was to replicate and extend previous work demonstrating selective impairment of semantic, but not episodic, memory in late versus early onset Alzheimer's disease (AD). Measures of episodic and semantic memory were administered to 12 pairs of patients; early (less than or equal to 62) and late (greater than or equal to 68) onset pairs were matched on dementia severity and education. As hypothesized, the groups did not differ on the three episodic memory measures but did on two of three semantic memory measures. In conjunction with prior research, these findings indicate that late onset AD is characterized by more profound impairment on measures of semantic processing.

Crystal structure of cleaved human alpha 1-antichymotrypsin at 2.7 A resolution and its comparison with other serpins.

The crystal structure of proteolytically modified human alpha 1-antichymotrypsin (ACT), a member of the serpin superfamily, has been solved by Paterson search techniques and refined to an R-factor of 18.0% at 2.7 A resolution with mean deviations from standard bond lengths and angles of 0.013 A and 3.1 degrees, respectively. The final model consists of 374 amino acid residues, 126 solvent molecules and five sugar residues. Asn70 could be identified unambiguously as a glycosylation site and Asn104 is probably also glycosylated. The structure of cleaved ACT is compared with cleaved alpha 1-antitrypsin (alpha 1 PI) and with plakalbumin, which are prototypical models for cleaved and intact serpins, respectively. Cleaved ACT is very similar to cleaved alpha 1 PI; in particular, it has strand s4A, which is liberated by proteolysis, inserted as the middle strand in beta-sheet A. ACT and alpha 1 PI differ locally only at sites of insertions, except at the segment s3C-turn-s4C, which is displaced by several angström units. This region of ACT is involved in DNA binding.

Maze learning in Alzheimer's disease.

Alzheimer's disease (AD) patients and normal elderly controls performed a block of 10 trials on a finger maze, followed by a 45-min period during which verbal learning measures were administered. Subjects then performed an additional 10 trials on the original maze, followed by 10 trials on a new maze. The AD patients and a subset of control subjects decreased mean completion time across Blocks 1 and 2, suggesting skill acquisition. Mean time on Block 3 was significantly less than mean time on Block 1, suggesting skill generalization. A subset of controls did not show the above pattern. The results of this study suggest that AD patients are able to acquire and generalize a cognitively mediated perceptual-motor skill.

Preserved word-stem-completion priming of semantically encoded information in Alzheimer's disease.

Alzheimer's disease (AD) patients and normal elderly control subjects completed 80 standardized sentence frames with single words, yielding a measure of semantic memory. Memory for best fit sentence endings was then tested either explicitly, with a forced-choice recognition task, or implicitly, with a word-stem-completion task. The patients completed fewer sentences with best fit word endings than did the control subjects. Explicit retention was markedly defective in the AD group, but word-stem completion was normal. The preserved word-stem completion in AD is discussed in terms of encoding operations and transfer-appropriate processing.

[Correlation between CT findings and clinical course in viral and bacterial meningoencephalitis]. / Korrelation zwischen CT-Befunden und klinischem Verlauf bei viralen und bakteriellen Meningoenzephalitiden.

The computed axial tomograms (CAT) of 50 patients with viral or bacterial meningoencephalitis are correlated with the clinical course, the laboratory data, and the EEG changes. The diagnostic value of CAT in the early diagnosis of herpes simplex encephalitis is of specific importance. Hypodense regions are demonstrated after the fifth day of illness in the temporal lobe. All other viral or bacterial meningoencephalitis cases have no specific changes on CAT examination compared with clinical or laboratory data. However, in localised encephalitis CAT may reveal hypodense regions. For follow-up studies of meningoencephalitis CAT is of important diagnostic value in demonstrating complications such as abscess or occlusive hydrocephalus.

[Watershed infarctions--a special type of infarction in cases with carotid artery stenosis or occlusion verified by CT and angiography (author's transl)]. / Der Grenzzoneninfarkt als besondere Infarktkonstellation bei Karotisinsuffizienz. Eine computertomographisch-angiographische Korrelationsstudie.

Watershed infarctions appear in the axial CT-sections mostly as stained or striated hypodense areas in the white matter of the parietal and seldom temporal region, without or with extension into the supply area of the adjacent cerebral arteries. We observed these changes in approximately 40% of our series with carotid artery stenosis or occlusion. These findings may be very subtle, and in such cases angiography should be performed.