Hematopoietin sub-family classification based on size, gene organization and sequence homology.

The hematopoietins constitute a family of structurally related proteins that includes many cytokines, growth factors and hormones. We propose a classification for hematopoietins based on their size, gene organization and sequences; in addition, we further suggest that three cytokines, IL-11, IL-12 alpha chain and IL-13, are hematopoietins, and we place them in specific subgroups.

The DECD box putative ATPase Sub2p is an early mRNA export factor.

Nuclear mRNA metabolism relies on the interplay between transcription, processing, and nuclear export. RNA polymerase II transcripts experience major rearrangements within the nucleus, which include alterations in the structure of the mRNA precursors as well as the addition and perhaps even removal of proteins prior to transport across the nuclear membrane. Such mRNP-remodeling steps are thought to require the activity of RNA helicases/ATPases. One such protein, the DECD box RNA-dependent ATPase Sub2p/UAP56, is involved in both early and late steps of spliceosome assembly. Here, we report a more general function of Saccharomyces cerevisiae Sub2p in mRNA nuclear export. We observe a rapid and dramatic nuclear accumulation of poly(A)(+) RNA in strains carrying mutant alleles of sub2. Strikingly, an intronless transcript, HSP104, also accumulates in nuclei, suggesting that Sub2p function is not restricted to splicing events. The HSP104 transcripts are localized in a single nuclear focus that is suggested to be at or near their site of transcription. Intriguingly, Sub2p shows strong genetic and functional interactions with the RNA polymerase II-associated DNA/DNA:RNA helicase Rad3p as well as the nuclear RNA exosome component Rrp6p, which was independently implicated in the retention of mRNAs at transcription sites. Taken together, our data suggest that Sub2p functions at an early step in the mRNA export process.

The interleukin-4 family of lymphokines.

Evidence has accumulated indicating that four T-cell derived lymphokines, interleukin-4, interleukin-5, granulocyte-macrophage colony stimulating factor and interleukin-3, are closely related. The genes encoding these lymphokines are clustered within a region of 1000 kb, the proteins have a common secondary and spatial organization, and their corresponding receptors are all members of the haemopoietin family of receptors.

Mitochondrial group II introns, cytochrome c oxidase, and senescence in Podospora anserina.

Podospora anserina is a filamentous fungus with a limited life span. It expresses a degenerative syndrome called senescence, which is always associated with the accumulation of circular molecules (senDNAs) containing specific regions of the mitochondrial chromosome. A mobile group II intron (alpha) has been thought to play a prominent role in this syndrome. Intron alpha is the first intron of the cytochrome c oxidase subunit I gene (COX1). Mitochondrial mutants that escape the senescence process are missing this intron, as well as the first exon of the COX1 gene. We describe here the first mutant of P. anserina that has the alpha sequence precisely deleted and whose cytochrome c oxidase activity is identical to that of wild-type cells. The integration site of the intron is slightly modified, and this change prevents efficient homing of intron alpha. We show here that this mutant displays a senescence syndrome similar to that of the wild type and that its life span is increased about twofold. The introduction of a related group II intron into the mitochondrial genome of the mutant does not restore the wild-type life span. These data clearly demonstrate that intron alpha is not the specific senescence factor but rather an accelerator or amplifier of the senescence process. They emphasize the role that intron alpha plays in the instability of the mitochondrial chromosome and the link between this instability and longevity. Our results strongly support the idea that in Podospora, "immortality" can be acquired not by the absence of intron alpha but rather by the lack of active cytochrome c oxidase.

Mutations in genes encoding the mitochondrial outer membrane proteins Tom70 and Mdm10 of Podospora anserina modify the spectrum of mitochondrial DNA rearrangements associated with cellular death.

Tom70 and Mdm10 are mitochondrial outer membrane proteins. Tom70 is implicated in the import of proteins from the cytosol into the mitochondria in Saccharomyces cerevisiae and Neurospora crassa. Mdm10 is involved in the morphology and distribution of mitochondria in S. cerevisiae. Here we report on the characterization of the genes encoding these proteins in the filamentous fungus Podospora anserina. The two genes were previously genetically identified through a systematic search for nuclear suppressors of a degenerative process displayed by the AS1-4 mutant. The PaTom70 protein shows 80% identity with its N. crassa homolog. The PaMdm10 protein displays 35.9% identity with its S. cerevisiae homolog, and cytological analyses show that the PaMDM10-1 mutant exhibits giant mitochondria, as does the S. cerevisiae mdm10-1 mutant. Mutations in PaTOM70 and PaMDM10 result in the accumulation of specific deleted mitochondrial genomes during the senescence process of the fungus. The phenotypic properties of the single- and double-mutant strains suggest a functional relationship between the Tom70 and Mdm10 proteins. These data emphasize the role of the mitochondrial outer membrane in the stability of the mitochondrial genome in an obligate aerobe, probably through the import process.

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P21 gene expression as an indicator for the activity of adenovirus-p53 gene therapy in non-small cell lung cancer patients.

Alterations in the tumor suppressor gene p53 lead to impaired cell cycle control, allowing for the development and growth of tumors. To restore a loss of p53 function, we performed a phase I study of intratumoral gene therapy with adenovirus expressing wild-type p53 in patients with non-small cell lung cancer carrying mutations in the p53 gene. Furthermore, in a phase II study, gene therapy was complemented with simultaneous cisplatin/vinorelbine treatment. Biopsies were obtained from all treated patients before and 24-48 hours after gene therapy to study changes in the expression of p53 target genes. We report here that in most of the cases, the target gene p21 was up-regulated, especially when injection of higher doses of p53-expressing adenovirus was combined with simultaneous chemotherapy, whereas Pig3, previously reported to be highly up-regulated by p53, generally did not show a clear increase. Interestingly, a clear p21 gene response was observed only in tumors showing stabilization or regression. We conclude that p21 appears to be up-regulated after adenovirus-mediated p53 gene transfer and is the most sensitive marker tested for biological response to gene therapy in the small cohort of non-small cell lung cancers that were studied.

Preclotting of knitted Dacron prosthesis. A scanning electron microscope study.

A scanning electron microscope study of preclotting on knitted Dacron prosthesis is reported. Five steps of the interaction are well identified: (1) before any blood contact (virgin Dacron), (2) during the first 3 minutes (fibrin and platelet aggregates), (3) fifth minute of contact (clotting), (4) 15 minutes of contact with heparinized blood (thin fibrin network), and (5) the following minutes (invasion of fibrin, which enmeshes blood cells).

Comparative study of DHBV DNA levels and endogenous DNA polymerase activity in naturally infected ducklings in France.

Duck hepatitis B virus (DHBV) was found in the serum of 1-6% of Pekin ducklings originated from French commercial flocks. The viremia was followed in the serum of 5 ducklings over a span of 3 mth by monitoring the levels of DHBV DNA and the endogenous DNA polymerase (DNAp) activity. The DHBV DNA levels in serum were quantified either by the DNA dot hybridization technique including counting of retained radioactivity, or by successive dilutions of each serum sample followed by DNA hybridization. The counting of the retained radioactivity was plotted on a curve and its evolution compared with that of viral DNAp activity. DHBV DNA levels in serum, estimated by both methods paralleled those of the DNAp activity, which peaked at the 4th or 5th week posthatch to decrease and fluctuate thereafter. Occasional discordance between DHBV DNA levels and the endogenous DNAp activity was observed, which could be correlated with the degree of repair of the single stranded gap of serum DHBV DNA. Parallel follow up studies comparing quantitative estimations of serum viral DNA and of DNAp activity, as presented here, may provide some clues for the understanding of the mechanisms involved in the establishment of the HEPA DNA virus carrier state. Such comparative studies may also be crucial for optimal monitoring of antiviral drugs in both human clinical trials and animal experimental studies.

Effect of cimetidine on aspirin-induced gastric hemorrhage in dogs.

Efficacy of cimetidine in the prevention of aspirin-induced gastric hemorrhage was evaluated, using 4 groups of 6 dogs given: Group 1--controls; group 2-7.5 mg of cimetidine/kg of body weight every 8 hours; group 3-7.5 mg of cimetidine/kg every 8 hours and 35 mg of nonbuffered aspirin/kg every 8 hours; and group 4-35 mg of nonbuffered aspirin/kg every 8 hours. All medication was given orally for 10 days at the time of feeding a commercial dry food. The gastric mucosa was evaluated endoscopically before treatment, on treatment day 5, and 36 hours after the final treatment. The dogs were given halothane inhalation anesthesia and were evaluated, using a grading system. Total 24-hour fecal hemoglobin (Hb) concentration was measured, using a quantitative fluorometric analysis for Hb-derived porphyrins. Control dogs and dogs given cimetidine only had no endoscopically visible gastric lesions and no increase in fecal Hb concentration. All dogs given aspirin or aspirin and cimetidine had a similar marked increase in endoscopically visible gastric hemorrhage and marked increases in fecal Hb concentration; however, there was no significant (P = 0.48) difference between the 2 groups. Seemingly, cimetidine given at an oral dosage of 7.5 mg/kg every 8 hours was not effective in preventing aspirin-induced gastric hemorrhage in clinically normal dogs.

Serum salicylate concentrations and endoscopic evaluation of the gastric mucosa in dogs after oral administration of aspirin-containing products.

The serum salicylate concentration produced by oral administration of plain aspirin and several aspirin-containing products given at 8-hour intervals for 7 treatments was measured in 36 laboratory-conditioned adult dogs. The dogs were randomly allotted to 6 groups of 6 dogs each: group 1 was given plain aspirin at a dosage of 25 mg/kg of body weight: group 2 was given plain aspirin at a dosage of 10 mg/kg; group 3 was given buffered aspirin at a dosage of 25 mg/kg; group 4 was given enteric-coated aspirin at a dosage of 25 mg/kg; group 5 was given buffered aspirin at a dosage of 25 mg/kg; and, group 6 was given a placebo. Serum salicylate concentration was measured at 2-hour intervals for the first 8 hours, and then at 8-hour intervals for the next 40 hours. Following the last dosing, serum salicylate concentration was measured at 2-hour intervals until 56 hours; the final 2 samples were measured at 64 and 72 hours. The effect of aspirin on the gastric mucosa was studied in 12 dogs, 3 each randomly selected from groups 1, 3, 4, and 5. The gastric mucosa of each dog was examined with a fiberoptic gastroscope 3 days before the beginning of treatment; lesions were not seen. The drugs were administered as described and the gastric mucosa of each dog was reexamined at 72 hours. Administration of the aspirin-containing products at 8-hour intervals resulted in sustained therapeutic serum salicylate concentrations (greater than 5 mg/dl) in all dogs, except those of group 2. The greatest fluctuation in serum salicylate concentration was found in dogs of group 4. Gastric lesions were seen only in the 3 dogs of group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of a fluorometric method for the quantitative assay of fecal hemoglobin in the dog.

Feces from 27 dogs were evaluated to establish baseline fecal hemoglobin (Hb) concentrations when the dogs were fed diets containing varying amounts of Hb. Fecal Hb concentration was measured, using a quantitative fluorometric assay that was based on the conversion of nonfluorescing Hb heme to fluorescing porphyrins. Mean fecal Hb concentration was 0.31 mg/g of feces when the dogs were fed a dry diet low in Hb. This corresponded to a daily fecal blood loss of 0.043 ml/kg of body weight. The fecal Hb concentration was directly related to the dietary Hb concentration. The average recovery of orally ingested blood was 41% in 4 dogs. This fluorometric assay quantitatively detected small amounts of gastrointestinal bleeding over a wide range of fecal Hb concentrations for which feces appeared normal. Results of this study establish dietary conditions necessary for quantitative evaluation of experimental and clinical gastrointestinal bleeding.

Fragmented medial coronoid process of the ulna in the dog.

Fragmented medial coronoid process of the ulna is an important cause of elbow dysplasia in the dog. Etiologic factors that have been identified include osteochondrosis, ulnar trochlear notch incongruity or dysplasia, and asynchronous growth of the radius and ulna. Treatment options that are discussed are conservative medical management, surgical removal of the coronoid fragments, and ulnar osteotomy or ostectomy. Prognosis is variable and depends on etiologic factors and response to therapy.

[A comparative study of the Doppler methods for evaluation of the degree of carotid artery stenosis. Continuous, pulsed, color Doppler]. / Etude comparative des méthodes Doppler pour l'évaluation du degré des sténoses carotidiennes. Doppler continu, pulsé, couleur.

OBJECTIVE: Compare various Doppler methods for the quantification of the degree of stenosis on 85 patients. METHOD: the following parameters were measured: maximal velocity (Vmax) inside the stenosis (PW), grades of spectral disturbances at the outlet of the stenosis (PW-CW), index of spectral disturbance (STI) at the outlet of the stenosis (PW-CW), ratio of velocities I(IC/CC) in internal and common carotid (PW), ratio of vessel cross section and residual lumen area (% STEN) by color Doppler. The reference method was the Grades of spectral disturbance and the index of stenosis measured post stenosis. (Method validated against angiography and pieces of endarterectomy.) The following comparisons were done; grades and STI by CW against grades and STI by PW, Vmax (PW) against grade and STI, % STEN (color) against grade and STI, % STEN (color) against Vmax (PW), I(IC/CC) (PW) against grade and STI, I(IC/CC) (PW) against Vmax. CONCLUSION: (a) grades or stenosis index : showed the best reproductibility; (b) a high correlation was found between the grades or stenosis index post stenosis measured by CW or PW; (c) Vmax was not proportional to the stenosis degree and showed large fluctuations for the same stenosis degree; (d) the I(IC/CC) showed large fluctuations for the same stenosis degree, the correlation was poor for this velocity ratio. Both Vmax and I(IC/CC) allow to detect only 2 groups of stenosis > 75% or > 90% in area; (e) color doppler over-estimate stenosis degree by approximately 20% but was more accurate and reproducible than Vmax. An appropriate procedure was designed to avoid this over estimation.

A higher inherent trait for fearfulness is associated with increased anxiety-like behaviours and diazepam sensitivity in Japanese quail.

This study tested whether lines of Japanese quails divergently selected for a fear response, the tonic immobility, might constitute a reliable bird model for studying anxiety. Previous studies demonstrated that the selection modifies the general underlying emotionality of the birds rather than exerting its effect only on tonic immobility. The behavioural effects of intraperitoneal injections of diazepam, an anxiolytic drug, were assessed in two lines of quail selected either for their short (STI) or long (LTI) duration of tonic immobility. Effects of diazepam were examined in two tests used for measuring emotionality in birds, the open field and the tonic immobility tests. After being placed in the centre of the open field, birds with a high emotionality (LTI quails) stayed longer in the centre of the apparatus than STI quail. Diazepam had anxiolytic effect in LTI birds as it increased the time spent in the outer area. This effect of diazepam appears to be selective because the drug has no effect on other behaviours such as distress calls or escape attempts. The drug has also no effect on the tonic immobility response in any of the two lines. These findings reveal an "anxiogenic" trait of LTI birds in the open field test that can be modulated by the administration of an anxiolytic drug. Therefore quails selected for LTI and STI represent a valuable model to study the mechanisms underlying anxiety in birds.