Association of FLAIR vascular hyperintensity and acute MCA stroke outcome changes with the severity of leukoaraiosis.

PURPOSE: The clinical significance of FLAIR vascular hyperintensity (FVH), a marker of collateral circulation in ischaemic stroke, remains controversial. We hypothesised that the association between FVH and outcomes varies with the severity of leukoaraiosis (LA), another marker of collaterals, and that their combined significance may vary with time. METHODS: We included 459 consecutive patients with middle cerebral artery (MCA) stroke. Proximal and distal FVHs were distinguished based on location. LA was divided into two grades, according to Fazekas scores of 0-2 and 3-6. Symptom-to-MRI time was divided into two categories: ≤ 14 days and ≥ 15 days. RESULTS: We found no difference in FVH proportion according to LA grade. Multivariate analysis revealed that LA and FVH status were independently associated with unfavourable outcomes (modified Rankin scale ≥ 2) in patients with symptom-to-MRI times ≤ 14 days (P = 0.008), but not in those with symptom-to-MRI times ≥15 days (P = 0.61). In the group with symptom-to-MRI times ≤14 days, patients with LA 3-6 and FVH(+) (OR, 3.044; 95% CI, 1.116-8.305) were more likely to have unfavourable clinical outcomes compared with patients with LA 0-2 and FVH(+) but not compared with those with LA 0-2 and FVH(-) or LA 3-6 and FVH(-). In addition, FVH location did not influence the relationship between FVH and outcomes. CONCLUSIONS: The association between FVH and outcomes was influenced by the degree of LA in the acute but not in the subacute and chronic stages of MCA infarction. FVH predicts clinical outcomes independently only in those with more extensive LA.

The Association between FLAIR Vascular Hyperintensity and Stroke Outcome Varies with Time from Onset.

BACKGROUND AND PURPOSE: FLAIR vascular hyperintensity has been recognized as a marker of collaterals in ischemic stroke, but the impact on outcome is still controversial. We hypothesized that the association between FLAIR vascular hyperintensity and outcome varies with time. MATERIALS AND METHODS: We included 459 consecutive patients with middle cerebral artery stroke and divided them into 3 groups by symptom-to-MR imaging time (group 1, ≤7 days; group 2, 8-14 days; group 3, ≥15 days). The FLAIR vascular hyperintensity score, ranging from 0 to 3 points, was based on territory distributions of different MCA segments. The associations between FLAIR vascular hyperintensity and outcome with time were analyzed qualitatively and quantitatively. RESULTS: No patients underwent MR imaging within 6 hours of onset. The proportion of FLAIR vascular hyperintensity (+) and severe stenosis or occlusion of MCA was not significantly dependent on time. In groups 1 and 2, FLAIR vascular hyperintensity (+) was significantly associated with larger lesions, the prevalence of flow injury, and unfavorable outcome (mRS ≥ 2). There were no such associations in group 3. Multiple logistic regressions demonstrated that FLAIR vascular hyperintensity (+) was an independent risk factor for unfavorable outcome in group 2. Infarction volume tended to increase with the increase of the distal FLAIR vascular hyperintensity score in groups 1 and 2, while declining in group 3. CONCLUSIONS: FLAIR vascular hyperintensity is associated with unfavorable outcome within 6 hours to 14 days of onset, while the wider distribution of distal FLAIR vascular hyperintensity may be favorable beyond 14 days of onset in MCA infarction. Symptom-to-MR imaging time should be considered when assessing the prognostic value of FLAIR vascular hyperintensity.

Biological properties of chimeric domain-deleted anticarcinoma immunoglobulins.

CC49 is a second-generation monoclonal antibody (MAb) that has high affinity for the tumor-associated pancarcinoma antigen tumor-associated glycoprotein-72. In clinical trials using gamma scanning, radiolabeled CC49 has facilitated the detection of more than 90% of carcinomas. We report here the development of a constant heavy-chain 2 (CH2) domain-deleted chimeric (c) CC49 MAb by transfecting an expression construct consisting of the CC49 murine variable region and a CH2 domain-deleted human IgG1 constant region into cCC49 kappa producing SP2/0 murine myeloma cells. As determined by SDS-PAGE, the intact cCC49 delta CH2 has a molecular weight of 153,000 and, under reducing conditions, molecular weights of 43,000 and 27,000. The plasma clearance and tumor-targeting properties of cCC49 delta CH2 were evaluated and compared with those of mouse/human chimeric forms cCC49 delta CH1 and intact cCC49. Previous studies have shown that the in vitro antigen-binding properties of cCC49 delta CH1 are similar to those of cCC49. Biodistribution studies reported here, using 131I-labeled cCC49 delta CH1 and 125I-labeled cCC49 in athymic mice bearing human colon carcinoma xenografts, demonstrated that both cMAbs localized to the tumor and cleared from the normal tissues similarly. However, in comparison with 125I-labeled cCC49, 131I-labeled cCC49 delta CH2 localized to tumors earlier and had a significantly lower percentage of the injected dose of cMAb/g (%ID/g) in normal tissues than cCC49. Immunoscintigraphy of 131I-labeled cCC49 delta CH2 and 125I-labeled cCC49 in athymic mice bearing human tumor xenografts demonstrated a clear image of the tumor by 24 h after i.v. administration of the delta CH2 cMAb versus the 72 h required for cCC49. Biodistribution studies using 177Lu-conjugated cCC49 delta CH1 and cCC49 showed no significant difference between the radiolocalization indices (% ID/g in tumor divided by % ID/g in normal tissue). 177Lu-conjugated cCC49 delta CH2, however, had lower % ID/g values in tumor xenografts and lower radiolocalization indices than either 177Lu-conjugated cCC49 delta CH1 or 177Lu-conjugated cCC49. Pharmacokinetic studies in non-tumor-bearing athymic mice using cCC49 delta CH1 and cCC49 revealed no significant difference between these cMAbs. However, the plasma clearance of cCC49 delta CH2 in non-tumor-bearing mice was significantly faster than that of cCC49. These results were similar when the cMAbs were labeled with either iodine or lutetium. In nonhuman primates, 131I-labeled cCC49 delta CH2 cleared significantly faster than 125I-labeled cCC49. The similar plasma clearance and tumor localization of cCC49 and cCC49 delta CH1 suggest that these two cMAbs may be used in similar clinical settings. However, because of the unique pharmacokinetics and tumor targeting of cCC49 delta CH2 versus cCC49 or cCC49 delta CH1, this chimeric immunoglobulin form may be useful in clinical settings that require efficient tumor targeting and rapid serum and whole-body clearance.

Nucleotide sequence of the genes encoded in early region 2b of human adenovirus type 12.

The nucleotide (nt) sequence of a cloned DNA segment containing the early 2b region of the class A adenovirus Ad12 has been determined. When compared to the corresponding region of Ad2 or Ad7, there is a high degree of nt and predicted amino acid (aa) sequence homology within the r-strand regions that encode the preterminal protein and the viral DNA polymerase. A gene coding region comparable to the Mr 13,600 gene product found in Ad2 can be identified; this hypothetical gene product shares 30% aa homology with its Ad2 counterpart and has a very similar hydropathy profile.

Expression of enzymatically active adenovirus DNA polymerase from cloned DNA requires sequences upstream of the main open reading frame.

Replication of human adenovirus (Ad) DNA requires three virus-encoded proteins that are coordinately transcribed from a single promoter at early times after infection. The mRNAs for two of these proteins, the preterminal protein (pTP) and the Ad DNA polymerase (Ad Pol), share several exons, including one encoded near Ad genome coordinate 39. Plasmids containing the putative exons that encode Ad Pol mRNA were constructed to determine if enzymatically active Ad Pol protein could be synthesized. An Ad Pol of 140 kDa was detected by immunoprecipitation with specific antibody and its enzymatic activity was confirmed by complementation of Ad DNA replication in vitro. In addition to an Ad2 DNA fragment from 24.7 to 9.2 map units which contains an open reading frame for a protein of 120 kDa, the HindIII-J fragment that encodes the exon at genome coordinate 39 can be shown to be essential for production of full-length (140 kDa), enzymatically active Ad Pol.

Study on the ecological distribution of alveolar Echinococcus in Hulunbeier Pasture of Inner Mongolia, China.

A study on the ecological distribution of alveolar Echinococcus was carried out in the Hulunbeier Pasture of Inner Mongolia, China during 1998 and 1999. Animals examined included wolves (Canis lupus), red foxes (Vulpes vulpes), sand foxes (Vulpes corsac), domestic dogs (Canis familiaris), Microtus brandti, Meriones unguiculatus, Citellus dauricus, Allactaga sibirica, Phodopus sungorus and Ochotona daurica. Three wolves were found to be infected with E. granulosus. Two sand foxes were infected with E. multilocularis. The majority of infections of alveolar echinococcus was found in M. brandti. Based on the structure of metacestodes found in the livers of naturally infected M. brandti, 3 main variants were observed. Type I had small alveolar cysts with thin cyst walls. Type II had a larger cyst with a thick cyst wall. Infection of laboratory mice with the gravid segments isolated from the naturally infected sand foxes led to the formation of mature Type I alveolar metacestodes in the lungs and Type II metacestodes in the livers of infected animals, respectively.