Impacts of hyper-homocysteinemia and white matter hyper-intensity in Alzheimer's disease patients with normal creatinine: an MRI-based study with longitudinal follow-up.

BACKGROUND: White matter hyper-intensities (WMHs) on magnetic resonance imaging (MRI) are commonly found in Alzheimer's disease (AD). Cerebro-vascular risk factors including plasma total homocysteine (tHcy) may result in WMHs. This study examined the association between tHcy and WMHs, and their effects on cognitive functions in AD patients over a two-year follow-up period. METHODS: One hundred and fifty-seven AD patients with a clinical dementia rating of 1 or 2 were enrolled and follow-up for two years. tHcy, biochemistry tests, and mini-mental state examination (MMSE) scores were collected. WMHs were visually rated on brain MRI and classified as deep white matter hyper-intensities (DWMHs) or peri-ventricular white matter hyper-intensities (PWMHs). MMSEs were performed every six months to survey cognitive decline. RESULTS: In the cross sectional study, tHcy was significantly associated with total WMHs especially in DWMHs even after adjusting for age and other cerebrovascular risk factors. Initial MMSE was inversely correlated with WMH severity but not with tHcy level. In the longitudinal analysis, no differences were found either in tHcy or WMHs score in the two AD groups defined by the cognitive decline rate. CONCLUSIONS: tHcy is an independent risk factor for developing moderate to severe DWMHs in AD but shows non-significant effect on cognitive performance. The close association between high WMH score and poor initial MMSE suggests an additive impact in AD. The long-term effect of elevated tHcy on cognitive decline was not conclusive in the two-year follow-up period.

Water exchange and permeability properties of the skin in three species of amphibious sea snakes (Laticauda spp.).

Evolutionary transitions between different environmental media such as air and water pose special problems with respect to skin permeability because of the dramatic changes in the driving gradients and nature of water exchange processes. Also, during the transitional periods prior to complete adaptation to a new medium, the skin is exposed to two very different sets of environmental conditions. Here, we report new data for transepidermal evaporative water loss (TEWL) and cutaneous resistance to evaporative water loss (R(s)) of sea snakes that are transitional in the sense of being amphibious and semi-terrestrial. We investigated three species of sea kraits (Elapidae: Laticaudinae) that are common to Orchid Island (Lanyu), Taiwan. Generally, R(s) of all three species is lower than that characteristic of terrestrial/xeric species of snakes measured in other taxa. Within Laticauda, R(s) is significantly greater (TEWL lower) in the more terrestrial species and lowest (TEWL highest) in the more aquatic species. Previously reported losses of water from snakes kept in seawater exhibit a reversed trend, with lower rates of loss in the more aquatic species. These data suggest selection for adaptive traits with respect to increasing exposure to the marine environment. Thus, a countergradient of traits is reflected in decreased TEWL in aerial environments and decreased net water efflux in marine environments, acting simultaneously in the three species. The pattern for TEWL correlates with ultrastructural evidence for increased lipogenesis in the stratum corneum of the more terrestrial species. The skin surfaces of all three species are hydrophobic. Species differences in this property possibly explain the pattern for water efflux when these snakes are in seawater, which remains to be investigated.

Postnatal ecdysis establishes the permeability barrier in snake skin: new insights into barrier lipid structures.

A competent barrier to transepidermal water loss (TEWL) is essential for terrestrial life. In various vertebrates, epidermal water barriers composed of lipids prevent excessive TEWL, which varies inversely with habitat aridity. Little is known, however, about the mechanisms and regulation of permeability relative to natal transition from the 'aqueous' environments of gestation to the 'aerial' environments of terrestrial neonates. We investigated newly hatched California king snakes Lampropeltis getula to test the hypothesis that the first ecdysis is important for establishing the barrier to TEWL. We found that skin resistance to TEWL increases twofold following the first postnatal ecdysis, corresponding with a roughly twofold increase in thickness and deposition of lamellar lipids in the mesos layer, the site of the skin permeability barrier in snakes. In addition, novel observations on lipid inclusions within the alpha layer of epidermis suggest that this layer has functional similarities with avian epidermis. It appears that emergence of the integument from embryonic fluids, and its subsequent pan-body replacement following contact with air, are essential for completion of barrier competence in the newborn. These conditions provide a potentially useful model for investigations on the mechanism of barrier formation. We also found that hatchling snakes are transiently endothermic, with skin temperatures elevated by approximately 0.6 degrees C above ambient air temperature during the period of barrier formation. Behaviourally, hatchlings showed a higher tendency to seek humid microenvironments before the first ecdysis than after. The degree of water movement across the integument might explain the switch from reclusive to dispersive behaviours associated with postnatal ecdysis in snakes.

Purification, sequencing, and phylogenetic analyses of novel Lys-49 phospholipases A(2) from the venoms of rattlesnakes and other pit vipers.

Basic phospholipase A(2) homologs with Lys49 substitution at the essential Ca(2+)-binding site are present in the venom of pit vipers under many genera. However, they have not been found in rattlesnake venoms before. We have now screened for this protein in the venom of rattlesnakes and other less studied pit vipers. By gel filtration chromatography and RP-HPLC, Lys49-phospholipase-like proteins were purified from the venoms of two rattlers, Crotalus atrox and Crotalus m. molossus, and five nonrattlers, Porthidium nummifer, Porthidium godmani, Bothriechis schlegelii, Trimeresurus puniceus, and Trimeresurus albolabris. Their N-terminal amino acid sequences were shown to be characteristic for this phospholipase subfamily. The purified basic proteins from rattlesnakes caused myonecrosis and edema in experimental animals. We have also cloned the cDNAs and solved the complete sequences of four novel Lys49-phospholipases from the venom glands of C. atrox, P. godmani, B. schlegelii, and Deinagkistrodon acutus (hundred-pace). Phylogenetic analyses based on the amino acid sequences of 28 Lys49-phospholipases separate the pitviper of the New World from those of the Old World, and the arboreal Asiatic species from the terrestrial Asiatic species. The implications of the phylogeny tree to the systematics of pit vipers, and structure-function relationship of the Lys49-phospholipases are discussed.

Phylogeny, taxonomy, and biogeography of the oriental pitvipers of the genus trimeresurus (reptilia: viperidae: crotalinae): a molecular perspective.

Based on sequence variation in 806 bp of the mitochondrial 12S rRNA gene, phylogenetic relationships were inferred for 14 species of Trimeresurus (sensu lato) including all East Asian members. Samples analyzed also included representatives of all assemblages of species that are frequently treated as separate genera except for T. mangshanensis, a type species of the recently described monotypic genus Ermia. Results support some previous accounts chiefly from morphological studies, such as distinct divergence of T. wagleri from the remainder, and monophyly of T. mucrosquamatus, T. flavoviridis, T. jerdonii, T. elegans and T. tokarensis. On the other hand, our results negated a putative close affinity of T. monticola and T. okinavensis, and indicated the sister relationship of the latter with T. gracilis. Phylogenetic relationships revealed in this study suggested that the genus Trimeresurus dispersed into the Ryukyu region at least three times, and that T. flavoviridis and T. tokarensis from the central Ryukyus constitute a relict clade.

Premarket evaluation of a commercial glycoprotein G-based enzyme immunoassay for herpes simplex virus type-specific antibodies.

A new commercial glycoprotein G-based enzyme immunoassay (gG-EIA) was compared with Western blotting (WB) for detection of herpes simplex virus type 1 (HSV-1) or HSV-2 type-specific antibodies in 193 serum samples. Sensitivity for HSV-1 was 95%; specificity was 96%. Sensitivity for HSV-2 was 98%; specificity was 97%. Twelve of 13 serum samples with equivocal gG-EIA results were serotyped by WB.

Advanced glycation end product (AGE): characterization of the products from the reaction between D-glucose and serum albumin.

We incubated bovine serum albumin (BSA) with glucose in an attempt to study how the advanced glycation end products (AGEs) are formed and what methods can be used for their identification and isolation. The reaction was monitored by boronated affinity gel, size exclusion and ion exchange chromatography, and chromatofocusing. Reaction products were also characterized by fluorescence measurement, fructosamine assay, and polyacrylamide gel electrophoresis (PAGE). Based on the measurement of AGE-associated fluorescence (excitation, 370 nm; emission, 440 nm) we found that the AGEs could be detected as early as after 3 days incubation. The fluorescence was always associated with the larger molecules of cross-linking product resulting from the reaction between BSA and glucose. The overall fluorescence intensity increased with incubation time and fluorescence of the highest intensity was found with the AGE product largest in size. As with the Amadori product, AGEs also bind to the boronated gel column but with an even higher affinity. Compared to the original albumin monomer AGE molecules are not only larger in size but also have lower isoelectric points and carry more negative charges. Both the size and the negative charges of AGEs continue to increase over time during incubation. This results in a group of cross-linking molecules heterogeneous in size and charge. These results will aid in both the isolation and selection of appropriate AGE molecules for the preparation of anti-AGE antibodies, calibrator, and control in the development of an AGE immunoassay.

[Treatment of olfactory neuroblastoma: a report of 14 cases].

Olfactory neuroblastoma is a rare malignant tumor arising from the nasal cavity. From 1982 to 1987 fourteen cases had been treated in this hospital. The average age was 34 years with a range from 15 to 65 years, male to female ratio was 1:1. At the time of diagnosis, 3 tumors were of kadish stage A-involvement of the nasal cavity only, 5 of stage B-involvement of the nasal cavity and one or more paranasal sinuses, and six of stage C-extension beyond the nasal cavity, including the orbit, base of skull or intracranial cavity, or metastasis to cervical nodes or distant sites. All were treated with radiation therapy and 7 also by surgery. The three and five-year survival rates were 50% and 30% respectively. Seven patients died, six because of distant metastases within one year. It shows that the disease is aggressive from the beginning, and tends to metastasize early. A treatment regimen for prophylactic cervical node irradiation combining chemotherapy is proposed.