A note on the relationship between fecal larval excretion and Protostrongylus rufescens lungworm burden in sheep.

The examination of feces for stages of parasitic helminths is the most widely used methodology for the intravital diagnosis in domestic animals of patent endoparasitism including pulmonary nematode infections. Although there is only little information on the relationship of lungworm larval excretion and corresponding parasite burdens, fecal larval counts are used as indirect measure ("biomarker") for the intensity of infection, for instance in anthelmintic efficacy studies. To assess the relationship between fecal larval and Protostrongylus rufescens parasite counts in sheep, log-transformed data of 14 naturally infected animals were analyzed. The larval excretion of the sheep was monitored in approximately weekly intervals over 6 weeks before lungworm recovery. Analyses were performed on the larval counts (at a single time point or counts averaged over several consecutive time points) relating to parasite counts. Fecal larval counts and the P. rufescens nematode burden (range, 17 to 406) were significantly and strongly correlated (p < 0.05 for all analyses; Spearman's r > 0.6) with the number of larvae excreted increasing with increasing lungworm burden. Subsequently performed regression analysis demonstrated a statistically significant strong linear relationship between P. rufescens worm and fecal larval counts (p < 0.01 for all analyses; R2, range 0.5094 to 0.8150). Analyses based on larval counts averaged over two or more consecutive time points resulted in higher Spearman's r and R2 compared with analyses based on single time point larval counts. Despite of some variability, the analyses indicate that fecal larval counts can be regarded as a useful measure of the P. rufescens burden in sheep.

Occurrence of the giant liver fluke, Fascioloides magna, in sympatric wild ungulates in one area in the Upper Palatinate Forest (northeastern Bavaria, Germany).

Associated with the spreading in (north)western direction of Fascioloides magna from its historic endemic area in Bohemia with its cervid hosts, unusual noticeable hepatic lesions (black-colored tissue, hemorrhage) were observed in deer harvested in hunting grounds and one deer farm located in the Upper Palatinate Forest close to the border to the Czech Republic, initially in the years of 2007 and 2009, respectively. Confirmation of the suspected diagnosis of F. magna infection in October 2011 prompted investigations on the occurrence of "fascioloidosis" among wild ungulates in that locality. From October 2011 to January 2014, livers from 89 cervids and two wild boars were examined for flukes. Thirty-seven livers (40.6%) harbored F. magna: 17 of 21 red deer, nine of 24 sika deer, six of eight fallow deer, four of 36 roe deer, one of two wild boars. Fluke burdens ranged from 2 up to 151 in red deer, from 2 up to 37 in fallow deer, and from 1 up to 7 in sika deer and in roe deer; one fluke was recovered from the liver of one wild boar. No other parasites were recovered from the livers. The rate of recovery of F. magna differed significantly (p < 0.001) among the species of deer (red deer, 81.0%; sika deer, 37.5%; fallow deer, 75.0%; roe deer, 11.1%) and between the age groups (< 1 year: 22.2%, 1 to 2 years: 26.0%, and > 2 years: 70.0%, respectively). There was no association (p > 0.1) between the rate of recovery of F. magna and the sex of the combined 80 deer of ≥ 1 year of age (male: 41.8% and female: 31.4%). The occurrence of F. magna in the wild ungulates in the Upper Palatinate Forest area in northeastern Bavaria is of epidemiological importance for the further spreading of the parasite into Germany with migrating deer.

Sex-specific association between obesity and self-reported falls and injuries among community-dwelling Canadians aged 65 years and older.

This study investigated the relationship between body mass index (BMI) and falls among community-dwelling elderly. Results indicate that obesity is associated with increased falls and there appears to be a sex-specific difference with obese men at higher risk of falling. Obesity is identified as a risk factor for falls in men. INTRODUCTION: The prevalence of falls, fall-related injuries, and obesity has increased over the last decade. The objectives of this study were to investigate sex-specific association and dose-response relationship between BMI and falls (and related injuries) among community-dwelling elderly. METHODS: Our study sample consisted of 15,860 adults aged 65 years or older (6399 men and 9461 women) from the 2008-2009 Canadian Community Health Survey-Healthy Aging (CCHS-HA). Falls, fall-related injuries, and BMI measures were self-reported. For both sex, dose-response curves presenting the relationship between BMI, falls, and fall-related injuries were first examined. Thereafter, multivariate logistic regression analyses were also performed to investigate these relationships after adjustment for potentially confounding variables. RESULTS: Of women, 21.7 % reported a fall and 16.9 % of men. The dose-response relationship between BMI and prevalence of falls showed that underweight and obese individuals reported falling more than normal and overweight individuals; this being more apparent in men than women. Finally, the dose relationship between BMI and prevalence of fall-related injuries showed that only obese men seem more likely to have sustained a fall-related injury. Results from the multivariate analysis showed that obesity in men was significantly associated with higher odds of falling odds ratio (OR) 1.33 (1.04-1.70) and was not significantly associated with higher odds of fall-related injuries OR 1.10 (0.66-1.84) over a 12-month period compared to normal weight men. For women, obesity was not significantly associated with higher fall prevalence OR 0.99 (0.79-1.25) and fall-related injuries OR 0.71 (0.51-1.00). CONCLUSION: Obesity is associated with self-reported falls, and there appears to be a sex-specific difference in elderly persons.

Multilocus sequence typing of canine Giardia duodenalis from South Eastern European countries.

Giardia duodenalis is a worldwide occurring protozoan that can infect various mammalian hosts. While living conditions are getting closer between pet animals and owners, there is discussion whether dogs may contribute to the transmission of these pathogens to humans. The present study was conducted in order to identify the Giardia assemblages in dogs from South Eastern Europe. For this purpose, 1645 faecal samples of household and shelter dogs from Albania, Bulgaria, Hungary, Macedonia, Romania and Serbia were tested for Giardia coproantigen by enzyme-linked immunosorbent assay (ELISA). A subset of 107 faecal samples demonstrating Giardia cysts by direct immunofluorescence assay (IFA) or microscopy (15-22 per country) plus 26 IFA-positive canine faecal samples from Croatia were used for DNA extraction and multilocus sequence typing with nested PCRs targeting five different gene loci: SSU rRNA, ITS1-5.8S-ITS2, beta giardin (bg), glutamate dehydrogenase (gdh) and triosephosphate isomerase (tpi). One third (33.7%) of the samples tested positive for Giardia antigen in the coproantigen ELISA. Shelter dogs were infected more frequently than household dogs (57.2 vs. 29.7%, p < 0.01). Amplification was obtained in 82.0, 12.8, 11.3, 1.5, and 31.6%, of the investigated samples at the SSU rRNA, bg, gdh and tpi loci and the ITS1-5.8S-ITS2 region, respectively. The dog-specific assemblages C and D were identified in 50 and 68 samples, respectively. The results demonstrate that G. duodenalis should be considered as a common parasite in dogs from South Eastern Europe. However, there was no evidence for zoonotic Giardia assemblages in the investigated canine subpopulation.

Associations between disability prevalence and local-area characteristics in a general community-living population.

BACKGROUND: Disability is understood to arise from person-environment interactions. Hence, heterogeneity in local-area characteristics should be associated with local-area variation in disability prevalence. This study evaluated the associations of disability prevalence with local-area socioeconomic status and contextual features. METHODS: Disability prevalence was obtained from the Canada census of 2001 for the entire province of Québec at the level of dissemination areas (617 individuals on average) based on responses from 20% of the population. Data on local-area characteristics were urban-rural denomination, social and material deprivation, active and collective commuting, residential stability, and housing quality. Associations between local-area characteristics and disability prevalence were assessed using multilevel logistic regressions. RESULTS: Disability was associated with local-area socioeconomic status and contextual characteristics, and heterogeneity in these factors accounted for urban-rural differences in disability prevalence. Associations between contextual features and disability prevalence were confounded by local-area socioeconomic status. Some associations between local-area socioeconomic status and disability prevalence were moderated by contextual characteristics. The importance of this effect modification is greater when expressed in terms of the absolute magnitude of disability than in the relative likelihood of disability. CONCLUSION: Explanation of rural-urban differences by the contribution of other local-area characteristics is consistent with the conceptualization of urban-rural categories as the reflection of spatially varying ensembles of compositional and contextual factors. Although local-area socioeconomic status explains most variability in disability prevalence, this study shows that contextual characteristics are relevant to analyses of the spatial patterning of disability as they predict spatial variations of disability, sometimes in interaction with socioeconomic status. This study demonstrates that absolute and relative perspectives on effect modification may lead to differing conclusions.

Bovine parafilariosis - New autochthonous cases from Germany and summary of recent reports from Europe.

Bovine parafilariosis is an emerging fly-borne disease in central Europe, characterized by seasonal occurrence of hemorrhagic exudations ('bleeding spots') from the end of winter to end of summer. In two cases from Germany reported here, one animal of a small herd in Bavaria and 20 animals on a farm in Baden-Württemberg presented bleeding spots from late March and late April 2020, respectively. Exudate samples from both cases were positive for larvated Parafilaria eggs. Examination of the skin and trimmed tissue after slaughter of the animal from Bavaria resulted in the collection of 11 nematodes (two males, eight females, one specimen in fragments). The animal's carcass presented typical yellow-greenish areas and bloody spots on the subcutaneous tissue of the flesh side of the skin. The nematodes were microscopically determined as Parafilaria bovicola. Basic morphometric measurements of two (one intact) male and six female nematodes are within the ranges of published data; length (male/female) 28.8/48.0-64.5 mm; width, 397.6 µm/430.7-527.6 µm; distance of cervical papillae to anterior end, 177.6/248.9-337.4; left spiculum/right spiculum (male), 365.3-379.4/149.5-180.3 µm; gubernaculum 45.0-48.1 µm; distance of vulva to anterior end (female), 37.3-66.0 mm. In order to gain information on P. bovicola in its vector, 91 cattle-visiting Musca autumnalis flies were collected from the affected animal in Bavaria (36 flies) and from co-pastured animals (55 flies) for PCR analysis and sequencing. A total of 14 flies were PCR-positive for filarial DNA, and sequencing of a fragment of the cox1 gene resulted in identification of P. bovicola (n = 10) and Thelazia gulosa (n = 5). This report presents further cases of bovine parafilariosis in Germany, provides morphometric data on male and female P. bovicola nematodes retrieved from cattle and identified DNA of P. bovicola and T.gulosa in M. autumnalis flies collected at a site of occurrence of bovine parafilariosis.

VRQ397 (CRAVKY): a novel noncompetitive V2 receptor antagonist.

Vasopressin type 2 receptor (V2R) exhibits mostly important properties for hydroosmotic equilibrium and, to a lesser extent, on vasomotricity. Drugs currently acting on this receptor are analogs of the natural neuropeptide, arginine vasopressin (AVP), and hence are competitive ligands. Peptides that reproduce specific sequences of a given receptor have lately been reported to interfere with its action, and if such molecules arise from regions remote from the binding site they would be anticipated to exhibit noncompetitive antagonism, but this has yet to be shown for V2R. Six peptides reproducing juxtamembranous regions of V2R were designed and screened; the most effective peptide, cravky (labeled VRQ397), was characterized. VRQ397 was potent (IC(50) = 0.69 +/- 0.25 nM) and fully effective in inhibiting V2R-dependent physiological function, specifically desmopressin-L-desamino-8-arginine-vasopressin (DDAVP)-induced cremasteric vasorelaxation; this physiological functional assay was utilized to avoid overlooking interference of specific signaling events. A dose-response profile revealed a noncompetitive property of VRQ397; correspondingly, VRQ397 bound specifically to V2R-expressing cells could not displace its natural ligand, AVP, but modulated AVP binding kinetics (dissociation rate). Specificity of VRQ397 was further confirmed by its inability to bind to homologous V1 and oxytocin receptors and its inefficacy to alter responses to stimulation of these receptors. VRQ397 exhibited pharmacological permissiveness on V2R-induced signals, as it inhibited DDAVP-induced PGI(2) generation but not that of cAMP or recruitment of beta-arrestin2. Consistent with in vitro and ex vivo effects as a V2R antagonist, VRQ397 displayed anticipated in vivo aquaretic efficacy. We hereby describe the discovery of a first potent noncompetitive antagonist of V2R, which exhibits functional selectivity, in line with properties of a negative allosteric modulator.

Cluster-state quantum computing enhanced by high-fidelity generalized measurements.

We introduce and implement a technique to extend the quantum computational power of cluster states by replacing some projective measurements with generalized quantum measurements (POVMs). As an experimental demonstration we fully realize an arbitrary three-qubit cluster computation by implementing a tunable linear-optical POVM, as well as fast active feedforward, on a two-qubit photonic cluster state. Over 206 different computations, the average output fidelity is 0.9832+/-0.0002; furthermore the error contribution from our POVM device and feedforward is only of O(10(-3)), less than some recent thresholds for fault-tolerant cluster computing.

A deprivation index for health planning in Canada.

Administrative databases in the Canadian health sector do not contain socio-economic information. To facilitate the monitoring of social inequalities for health planning, this study proposes a material and social deprivation index for Canada. After explaining the concept of deprivation, we describe the methodological aspects of the index and apply it to the example of premature mortality (i.e. death before the age of 75). We illustrate variations in deprivation and the links between deprivation and mortality nationwide and in different geographic areas including the census metropolitan areas (CMAs) of Toronto, Montréal and Vancouver; other CMAs; average-size cities, referred to as census agglomerations (CAs); small towns and rural communities; and five regions of Canada, namely Atlantic, Quebec, Ontario, the Prairies and British Columbia. Material and social deprivation and their links to mortality vary considerably by geographic area. We comment on the results as well as the limitations of the index and its advantages for health planning.

The alpha1-fetoprotein locus is activated by a nuclear receptor of the Drosophila FTZ-F1 family.

The alpha1-fetoprotein (AFP) gene is located between the albumin and alpha-albumin genes and is activated by transcription factor FTF (fetoprotein transcription factor), presumed to transduce early developmental signals to the albumin gene cluster. We have identified FTF as an orphan nuclear receptor of the Drosophila FTZ-F1 family. FTF recognizes the DNA sequence 5'-TCAAGGTCA-3', the canonical recognition motif for FTZ-F1 receptors. cDNA sequence homologies indicate that rat FTF is the ortholog of mouse LRH-1 and Xenopus xFF1rA. Rodent FTF is encoded by a single-copy gene, related to the gene encoding steroidogenic factor 1 (SF-1). The 5.2-kb FTF transcript is translated from several in-frame initiator codons into FTF isoforms (54 to 64 kDa) which appear to bind DNA as monomers, with no need for a specific ligand, similar KdS (approximately equal 3 x 10(-10) M), and similar transcriptional effects. FTF activates the AFP promoter without the use of an amino-terminal activation domain; carboxy-terminus-truncated FTF exerts strong dominant negative effects. In the AFP promoter, FTF recruits an accessory trans-activator which imparts glucocorticoid reactivity upon the AFP gene. FTF binding sites are found in the promoters of other liver-expressed genes, some encoding liver transcription factors; FTF, liver alpha1-antitrypsin promoter factor LFB2, and HNF-3beta promoter factor UF2-H3beta are probably the same factor. FTF is also abundantly expressed in the pancreas and may exert differentiation functions in endodermal sublineages, similar to SF-1 in steroidogenic tissues. HepG2 hepatoma cells seem to express a mutated form of FTF.

Functional analysis of developmentally regulated chromatin-hypersensitive domains carrying the alpha 1-fetoprotein gene promoter and the albumin/alpha 1-fetoprotein intergenic enhancer.

During liver development, the tandem alpha 1-fetoprotein (AFP)/albumin locus is triggered at the AFP end and then asymmetrically enhanced; this is followed by autonomous repression of the AFP-encoding gene. To understand this regulation better, we characterized the two early developmental stage-specific DNase I-hypersensitive (DH) sites so far identified in rat liver AFP/albumin chromatin: an intergenic DH-enhancer site and the AFP DH-promoter site. Mutation-transfection analyses circumscribed the DH-enhancer domain to a 200-bp DNA segment stringently conserved among species. Targeted mutations, DNA-protein-binding assays, and coexpression experiments pinpointed C/EBP as the major activatory component of the intergenic enhancer. Structure-function relationships at the AFP DH-promoter site defined a discrete glucocorticoid-regulated domain activated cooperatively by HNF1 and a highly specific AFP transcription factor, FTF, which binds to a steroid receptor recognition motif. The HNF1/FTF/DNA complex is deactivated by glucocorticoid receptors or by the ubiquitous factor NF1, which eliminates HNF1 by competition at an overlapping, high-affinity binding site. We propose that the HNF1-NF1 site might serve as a developmental switch to direct autonomous AFP gene repression in late liver development. We also conclude that the intergenic enhancer is driven by C/EBP alpha primarily to fulfill albumin gene activation functions at early developmental stages. Factor FTF seems to be the key regulator of AFP gene-specific functions in carcinoembryonic states.

Material and social deprivation and health and social services utilisation in Québec: a local-scale evaluation system.

Very few studies have employed local-scale analyses to evaluate how well primary health care and social services reach the most socially and economically deprived individuals. This paper describes a project, conducted in close partnership with decision-makers and practitioners at selected local community service centres (in French, CLSCs) in Quebec, Canada, that developed a system for assessing primary care and social services utilisation by applying deprivation levels defined at the local scale (i.e., according to the distribution of deprivation in individual CLSC service areas). More than 25 years ago, Québec started setting up a province-wide network of publicly financed CLSCs whose mission was to offer first-line health and social services at the local level. Now approximately one Quebecer in four receives at least one service a year from a CLSC. The evaluation system presented in this article is built on deprivation profiles for each CLSC service area and comprises maps, relative indices of service utilisation, and an interpretation framework that facilitates the integration of new data into the decision-making and services planning processes. Study results show that deprivation levels, when defined using local perspectives, correspond more closely to decision-makers' perceptions, that relative indices are sensitive to key determinants of services provision and utilisation, and that the interpretation framework is useful for reassessing intervention strategies.

[Cognitive disorders in multiple sclerosis]. / Les troubles cognitifs au cours de la sclérose en plaques.

Forty to sixty percent of patients with multiple sclerosis (MS) have cognitive dysfunction. The frequency of cognitive disturbances according to the clinical form is not completely understood and the natural history of these disorders has not been extensively studied. Cognitive deficits can be detected in early stages of the disease. Their frequency increases from clinically isolated syndromes, to relapsing-remitting and secondary progressive MS. Cognitive abnormalities are frequently observed also in primary progressive MS. The most frequently impaired functions are information processing speed, attention and memory. Dementia is uncommon but may disclose the disease. Diffuse cerebral injury, assessed by magnetic resonance imaging, contributes to cognitive dysfunction in MS, probably by interrupting connecting fibers between neuronal networks involved in these cognitive functions. Compensatory mechanisms may occur at early stages but they are limited by extension of brain injury.

[Vulvar lichen planus in children]. / Lichen plan vulvaire chez l'enfant.

BACKGROUND: Lichen planus is less common in children about in adults and mostly affects the skin. CASE REPORT: A 9-year-old girl was referred for a purplish blue and violaceous, unilateral and asymptomatic vulvar lesion noted 4 months earlier and stable. Histopathologic examination showed typical features of lichen planus. She responded well and rapidly with topical steroids. DISCUSSION: We report the first case of vulvar lichen planus in a little girl. Mucosal involvement is uncommon in children with lichen planus and genital localisation is extremely rare. Vulvar lichen sclerosis is the principal differential diagnosis. The risk of vulvar synechia and development of vulvar carcinomas warrants regular long-term follow-up.

Acaricide treatment prevents adrenocortical hyperplasia as a long-term stress reaction to psoroptic mange in cattle.

In cattle, infestation with Psoroptes ovis mites may cause severe dermatitis (psoroptic mange) which compromises the health and welfare of the animals and may lead to significant economic losses. To investigate yet undocumented effects of psoroptic mange mite infestations and how successful therapy promotes animal health, the present study examined alterations of the skin, lymph nodes and adrenal glands of P. ovis infested Fleckvieh (Simmental) bulls treated with either ivermectin long-acting injection (IVM LAI; IVOMEC(®) GOLD, Merial; 3.15% ivermectin w/v) or saline (n=16 each). Approximately 8 weeks subsequent to experimental infestation with P. ovis, the bulls had developed mange and were administered either IVM LAI or saline once at 1 mL/50 kg body weight by subcutaneous injection. Mite counts were conducted in weekly intervals for determination of efficacy of treatment, and following humane euthanasia of the animals 8 weeks after treatment, skin samples from affected (mangy or previously mangy) and unaffected areas, prescapular lymph nodes and adrenal glands were collected for gross and pathohistological examination. In addition, four age-matching, uninfested Simmental bulls were sampled as controls for comparison. No P. ovis mites were detected on any IVM LAI-treated bull after 28 days following treatment whereas saline-treated bulls maintained infestation throughout the study. At sampling (approximately 16 weeks after experimental infestation and 8 weeks following saline or IVM LAI treatment), saline-treated bulls displayed a severe, exsudative dermatitis with significantly increased skin thickness and inflammatory cell infiltration, significantly enlarged, hyperplastic prescapular lymph nodes, as well as significantly increased adrenal gland weights and volumes as compared to P. ovis-infested, IVM LAI-treated bulls and uninfested controls. Quantitative stereological analysis revealed that the adrenal gland enlargement in P. ovis-infested, saline-treated bulls was due to a selective increase of the volume of the zona fasciculata in the adrenal cortex. Compared to uninfested controls and P. ovis-infested, IVM LAI-treated bulls, the number of epithelial cells in the zona fasciculata was significantly increased in P. ovis-infested, saline-treated bulls, while the zona fasciculata cell volumes did not differ between the three groups of cattle. While the single point determination of serum cortisol concentrations did not reveal significant differences between the three groups of cattle at tissue sampling, the hyperplastic growth of the adrenal cortex in the P. ovis-infested, saline-treated bulls provides morphologic evidence that a chronic stress reaction is one consequence of mange mite infestations that can be prevented by efficacious acaricidal treatment.

Expression of HIV-1 in the cerebrospinal fluid detected by the polymerase chain reaction and its correlation with central nervous system disease.

The polymerase chain reaction (PCR) was used to detect HIV-1 sequences (gag, pol, and env) in the cerebrospinal fluid (CSF) and serum samples from 53 HIV-1-positive patients and the results correlated with clinical evidence of neurological disease. Twenty-three out of 24 patients with neurological disease had HIV-1-specific sequences in CSF compared with four out of 20 asymptomatic patients who had no evidence of neurological involvement. The detection of HIV RNA sequences by PCR in the CSF of HIV-positive patients may provide early, rapid and direct evidence of neurological involvement in asymptomatic subjects.

HIV-1 and HIV-2 dual infection: lack of HIV-2 provirus correlates with low CD4+ lymphocyte counts.

OBJECTIVE: We conducted this study to genetically characterize dual infection in individuals demonstrating a dual serological profile. METHODS: All subjects were first evaluated by immunoblot for antibody reactivity to the major viral antigens for HIV-1 and HIV-2. Sera were judged to be dual-seropositive if they reacted with strong and equal intensity with the envelope antigens of both HIV-1 and HIV-2 and were confirmed with type-specific recombinant env peptides. We used nested polymerase chain reaction (PCR) to amplify proviral gag and env sequence from peripheral blood mononuclear cell (PBMC) DNA from HIV-1- and HIV-2-infected individuals. Positive amplification was detected after Southern blot hybridization. RESULTS: Plasmid dilution and mixing showed equivalent sensitivity of HIV-1 and HIV-2 primers that was not altered by heterologous target sequences. The DNA PCR showed 100% sensitivity and specificity for detection of monotypic HIV infection. Serologically defined HIV-dual reactives were evaluated by this assay, with 100% detection in female sex workers (21 out of 21), but only 38.5% detection (five out of 13) in hospitalized patients; all being HIV-1 positive only. The lack of HIV-2 proviral signal was significantly correlated with low CD4+ lymphocyte counts (Pvalue = 0.04). CONCLUSION: The results suggest that HIV dual infection may not be a static condition. Levels of HIV-2 may decrease with disease progression or sequester in tissue reservoirs; our results may also suggest that HIV-1 effectively overgrows HIV-2 in the dually exposed host individual.

Three novel point mutations in the keratinocyte transglutaminase (TGK) gene in lamellar ichthyosis: significance for mutant transcript level, TGK immunodetection and activity.

We have investigated 8 patients from 7 unrelated families with lamellar ichthyosis (LI) for defects in the keratinocyte transglutaminase (TGK) gene. We have characterized three novel homozygous mutations and a previously reported splice acceptor site mutation. One patient showed a C-to-T change in the binding site for the transcription factor Sp1 within the promoter region. Another patient had a Gly 143-to-Glu mutation in exon 3 and a third patient, affected with a particular form of LI sparing the four limbs, demonstrated a Val382-to-Met mutation within exon 7. These three patients exhibited drastically reduced transglutaminase activity and an absence of detectable TGK polypeptide, as assessed by immunofluorescence and immunoblotting. Northern blot analysis showed that the Sp1 site mutation was associated with profound reduction of TGK transcript levels whereas normal transcript levels were observed for the two missense mutations. We hypothesize that the Sp1 site mutation impairs transcription of the TGK gene, whereas the two missense mutations induce structural changes leading to protein instability. Linkage to TGK was excluded in another family and no evidence for TGK defect was found in 3 other patients. These results further support the involvement of TGK in some patients with LI. They identify a TGK mutation as a cause for non-generalized LI and further delineate the molecular mechanisms underlying TGK deficiency in LI.

Identification of rat alpha-albumin and cDNA cloning of its human ortholog.

A rat alpha-albumin mRNA encodes an 80-kDa plasma protein (approx. 20 micrograms/ml in adult rat serum). Its 2-kb human ortholog displays extensive ligand-binding core sequence homology, but striking divergence in the C-terminal domain.