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Biomedical subjects

M Victor

Publications and source records attributed to M Victor.

At least 19 recordsLinked to original sources
PubMed2001

A POP-1 repressor complex restricts inappropriate cell type-specific gene transcription during Caenorhabditis elegans embryogenesis.

In Caenorhabditis elegans, histone acetyltransferase CBP-1 counteracts the repressive activity of the histone deacetylase HDA-1 to allow endoderm differentiation, which is specified by the E cell. In the sister MS cell, the endoderm fate is prevented by the action of an HMG box-containing protein, POP-1, through an unknown mechanism. In this study, we show that CBP-1, HDA-1 and POP-1 converge on end-1, an initial endoderm-determining gene. In the E lineage, an essential function of CBP-1 appears to be the activation of end-1 transcription. We further identify a molecular mechanism for the endoderm-suppressive effect of POP-1 in the MS lineage by demonstrating that POP-1 functions as a transcriptional repressor that inhibits inappropriate end-1 transcription. We provide evidence that POP-1 represses transcription via the recruitment of HDA-1 and UNC-37, the C.elegans homolog of the co-repressor Groucho. These findings demonstrate the importance of the interplay between acetyltransferases and deacetylases in the regulation of a critical cell fate-determining gene during development. Furthermore, they identify a strategy by which concerted actions of histone deacetylases and other co-repressors ensure maximal repression of inappropriate cell type-specific gene transcription.

Animals↗
PubMed2000

Food and metabolic signalling defects in a Caenorhabditis elegans serotonin-synthesis mutant.

The functions of serotonin have been assigned through serotonin-receptor-specific drugs and mutants; however, because a constellation of receptors remains when a single receptor subtype is inhibited, the coordinate responses to modulation of serotonin levels may be missed. Here we report the analysis of behavioural and neuroendocrine defects caused by a complete lack of serotonin signalling. Analysis of the C. elegans genome sequence showed that there is a single tryptophan hydroxylase gene (tph-1)-the key enzyme for serotonin biosynthesis. Animals bearing a tph-1 deletion mutation do not synthesize serotonin but are fully viable. The tph-1 mutant shows abnormalities in behaviour and metabolism that are normally coupled with the sensation and ingestion of food: rates of feeding and egg laying are decreased; large amounts of fat are stored; reproductive lifespan is increased; and some animals arrest at the metabolically inactive dauer stage. This metabolic dysregulation is, in part, due to downregulation of transforming growth factor-beta and insulin-like neuroendocrine signals. The action of the C. elegans serotonergic system in metabolic control is similar to mammalian serotonergic input to metabolism and obesity.

Amino Acid Sequence↗
PubMed1998

Expression levels of heat shock factors are not functionally coupled to the rate of expression of heat shock genes.

The expression patterns of two mammalian heat shock factors (HSFs) were analysed in cell systems known to reflect an altered heat shock response. For being able to discriminate between the two closely related factors HSF 1 and HSF 2, specific cDNA sequences were cloned and used to generate antisense RNAs as hybridization probes. In general, in various cell lines expression of the two heat shock factors was clearly different. These expression patterns of the HSF genes were not influenced by retinoic acid-induced differentiation of human NT2 and mouse F9 teratocarcinoma cells. Generally, HSF 2 expression was extremely low, whereas the significantly higher expression of HSF 1 revealed cell specific differences. The highest expression rates of both HSFs were observed in 293 cells. To examine whether these high levels are involved in the constitutive expression of heat shock genes in these cells, we analysed the binding pattern of 293 cell proteins to the heat shock elements (HSEs). As with other cells, HSE-binding activity in 293 cells was only observed after heat shock treatment. This points to an HSE-independent way for high level expression of heat shock genes in these cells.

Animals↗
PubMed1997

Basal level transcription of the human hsp86 gene is directed by intron-based elements.

BACKGROUND: The heat shock response includes the syntheses of three major size-classes of heat shock proteins (hsps) designated as class 20, 70 and 90 hsps, respectively. In contrast to the class 20 and 70 hsp genes, those coding for the class 90 hsps are already actively transcribed in the non-induced state. RESULTS: We have shown that the increased basal level transcription of the human hsp86 gene depends on the presence of the first intron. Furthermore, intron 1 of the hsp86 gene was also capable of conferring increased basal level transcription on the human hsp70 promoter. Finally, the intron I-based sequence elements of the hsp86 gene mediated an effective rescue of 5'-truncated hsp70 and hsp86 promoters. In contrast, such a rescue of inactivated promoters was not obtained with the viral SV40 gene enhancer which is often also capable of stimulating basal level expression. CONCLUSIONS: Element(s) which direct the basal transcription of the human hsp86 gene at normal physiological temperatures are located within the first intron of the gene. It is conceivable that this intron-dependent activation of basal hsp86 transcription reflects a fundamental requirement for this protein in the context of cellular growth and metabolism under non-stress conditions.

HeLa Cells↗
PubMed1994

Alcoholic dementia.

At least four distinct cerebral diseases--Wernicke-Korsakoff, Marchiafava-Bignami, pellagrous encephalopathy, and acquired hepatocerebral degeneration--have a close association with chronic alcoholism. Each is characterized by a distinctive pathologic change and a reasonably well-established pathogenesis; in each the role of alcohol in the causation is secondary. The question posed in this review is whether there is, in addition to the established types of dementia associated with alcoholism, a persistent dementia attributable to the direct toxic effects of alcohol on the brain--i.e., a primary alcoholic dementia. The clinical, psychologic, radiologic, and pathologic evidence bearing on this question is critically reviewed. None of the evidence permits the clear delineation of such an entity. The most serious flaw in the argument for a primary alcoholic dementia is that it lacks a distinctive, well-defined pathology, and it must remain ambiguous until such time as its morphologic basis is established.

Alcohol Amnestic Disorder↗
PubMed1993

Persistent altered mentation due to ethanol.

It has long been appreciated that the chronic abuse of alcohol may lead to a deterioration of intellect, personality, and behavior. Some of the ways in which this comes about are reasonably well established. The dementing diseases of Wernicke-Korsakoff syndrome, pellagra, the nonfamilial form of hepatocerebral degeneration, Marchiafava-Bignami disease, and alcoholic dementia and their relationships to chronic alcoholism are discussed in this article.

Alcoholism↗
PubMed1988

Bioavailability and pharmacokinetics of oxazepam.

Six healthy volunteers received oxazepam 15 mg i.v. and orally at an interval of at least one week. The kinetic variables of i.v. oxazepam were: elimination half-life (t1/2 beta) 6.7 h, total clearance (CL) 1.07 ml.min-1.kg-1, volume of distribution (Vc) 0.27 l.kg-1 (0.21-0.49) and volume of distribution at steady-state (Vss) 0.59 l.kg-1. The intravenous disposition of unbound oxazepam was characterized by a clearance of 22.5 ml.min-1.kg-1 and a distribution volume of 12.3 l.kg-1. After oral oxazepam the peak plasma level was reached in 1.7 to 2.8 h. The plasma t1/2 beta at 5.8 h was not significantly different from the i.v. value. Absorption was almost complete, with a bioavailability of 92.8%. Urinary recovery was 80.0 and 71.4% of the dose after intravenous and oral administration, respectively. Renal clearance (CLR) of the glucuronide metabolite was 1.10 ml.min-1.kg-1 (0.98-1.52). Oxazepam was extensively bound to plasma protein with a free fraction of 4.5%.

Administration, Oral↗
PubMed1987

Respiratory burst facilitates the digestion of Escherichia coli killed by polymorphonuclear leukocytes.

We examined factors that may limit degradation of bacterial protein of Escherichia coli S15 killed by polymorphonuclear leukocytes (PMN). Both human and rabbit PMN degraded up to 40% of [14C]amino acid-labeled protein of ingested and killed E. coli in 2 h as determined by loss of acid-precipitable radioactivity. In contrast, equally bactericidal broken-PMN preparations or isolated granules degraded only about 10% of bacterial protein regardless of pH. To determine whether activation of the respiratory burst contributes to digestion, we compared degradation by intact PMN in room air and under N2. Depletion of O2 by N2 flushing had no effect on the bactericidal activity of either human or rabbit PMN but reduced degradation by approximately 50%. Protein degradation during phagocytosis was also reduced in the presence of cyanide or azide, inhibitors of myeloperoxidase (MPO). PMN of two patients with chronic granulomatous disease ingested and killed E. coli S15 as well as did normal PMN but degraded bacterial protein as did normal PMN incubated under N2. The low degradative activity of PMN disrupted by sonication could be raised to nearly the level of intact PMN incubated in room air by preincubation of the PMN with 10(-7) M formyl-methionyl-leucyl-phenylalanine (fMLP) before sonication and by pretreatment of E. coli with MPO. Depletion of O2 or chloride during these preincubations with formyl-methionyl-leucyl-phenylalanine respectively, virtually abolished and markedly diminished stimulation of bacterial protein degradation. We conclude that enhanced MPO-mediated O2 metabolism of intact PMN plays a role in the digestion of killed E. coli.

Animals↗
PubMed1987

Alcohol withdrawal seizures.

Seizures that occur in relation to alcohol withdrawal, following a period of prolonged intoxication in serious alcoholics, constitute a special syndrome with important prognostic and therapeutic implications. Inpatient management is desirable to eliminate other causes of seizures that occur for the first time in adult life and because such patients are at substantial risk for additional seizures and the development of delirium tremens. Drug therapy with benodiazepines may be effective during the withdrawal period but long-term anticonvulsant treatment is of no value.

Alcohol Withdrawal Delirium↗
PubMed1985

Killing of gram-negative bacteria by neutrophils: role of O2-independent system in intracellular killing and evidence of O2-dependent extracellular killing.

For many strains of these two bacterial species, ingested bacteria are efficiently killed by O2-independent mechanisms. Intracellular killing depends not on 2de novo generation of toxic products of the respiratory burst but rather on intracellular delivery to pre-existing cytotoxic proteins. The principal O2- independent bactericidal system toward these bacteria appears to be BPI which rapidly binds to ingested bacteria and whose discrete action closely resembles the initial lesions produced by the intact neutrophil. In addition, at least for one strain of E. coli (S15), extracellular bacteria can be killed in an O2- dependent fashion.

Animals↗
PubMed1985

Oxygen-independent intracellular and oxygen-dependent extracellular killing of Escherichia coli S15 by human polymorphonuclear leukocytes.

Effective killing of bacteria by polymorphonuclear leukocytes (PMN) is generally assumed to require intracellular sequestration and, depending on the bacterial species, can be both O2-dependent or O2-independent. Killing of several strains of Salmonella typhimurium and Escherichia coli by rabbit PMN does not require O2 and is apparently due to a granule-associated bactericidal/permeability-increasing protein (BPI) present in rabbit and human PMN. In this study we examined the O2 dependence of the killing of E. coli (S15) by human PMN. Ingested and noningested E. coli were separated by centrifugation after incubation with PMN in room air or under N2. In the presence of heat-treated serum approximately 50% of E. coli (10 bacteria/PMN) were taken up by PMN and rapidly (5-15 min) killed both in room air and under N2. The remaining extracellular bacteria (approximately 50%) were killed during 30-60 min of incubation in room air but not under N2. When uptake of E. coli by PMN was increased to approximately 80% by the use of C6-depleted serum (retaining heat-labile opsonins), bacterial survival under N2 was reduced from 54 +/- 7.6% to 13 +/- 5.5%. PMN from a patient with chronic granulomatous disease killed PMN-associated but not extracellular E. coli. BPI was detected, by indirect immunofluorescence, on the surface of PMN-associated E. coli within 5 min of incubation of E. coli with PMN both in room air and under N2. In contrast, at no time was BPI detected on the surface of extracellular E. coli, indicating that the non-PMN-associated E. coli had not been previously ingested. Thus, killing of ingested E. coli S15 by human as well as rabbit PMN does not require O2 and appears to be BPI-mediated. However, when ingestion is limited, extracellular bacteria can also be killed but principally by O2-dependent mechanisms.

Antimicrobial Cationic Peptides↗
PubMed1984

Calcification of the tricuspid anulus diagnosed by two-dimensional echocardiography.

An 84-year-old female who previously underwent repair of an atrial septal defect had evidence of increased reflectiveness of the posterior tricuspid anulus in the apical four-chamber view and the right ventricular two-chamber view. In addition, the inferior vena cava was dilated and during contrast echocardiography, contrast echoes appeared during systole suggesting tricuspid regurgitation. Tricuspid annular calcification was confirmed by fluoroscopic examination. Tricuspid annular calcification is extremely rare and in the present series occurred in 1 of 80 patients with mitral annular calcification. Lateral resolution echoes from a calcified aortic valve and echoes originating from a calcified right coronary artery have to be distinguished from tricuspid annular calcification.

Aged↗
PubMed1984

An epidemiologic and clinical evaluation of Guillain-Barré syndrome reported in association with the administration of swine influenza vaccines.

As a result of a court order, computerized summaries of approximately 1,300 cases reported as Guillain-Barré syndrome by state health departments to the Centers for Disease Control during the intensive national surveillance instituted following the swine influenza vaccination program in 1976-1977 became available for further study. Although the data were not uniformly adequate to confirm the diagnosis of Guillain-Barré syndrome, they were sufficient to enable classification according to extent of motor involvement. Vaccinated cases with "extensive" paresis or paralysis occurred in a characteristic epidemiologic pattern closely approximated by a lognormal curve, suggesting a causal relationship between the disease and the vaccine. Cases with "limited" motor involvement showed no such pattern, suggesting that this group included a substantial proportion of cases which were unrelated to the vaccine. The effect attributed to the vaccine lasted for at least six weeks and possibly for eight weeks but not longer. The relative risk of acquiring "extensive" disease over a six-week period following vaccination ranged from 3.96 to 7.75 depending on the particular baseline estimate of expected normal or endemic incidence that was chosen. Correspondingly, the number of cases that could be attributed to the vaccine over the six-week period ranged from 211 to 246, or very slightly higher over an eight-week period if the lowest baseline estimate was used. The total rate of Guillain-Barré syndrome cases attributed to prior use of the vaccine was 4.9 to 5.9 per million vaccinees.

Centers for Disease Control and Prevention, U.S.↗
PubMed1984

The role of lipopolysaccharides in the action of the bactericidal/permeability-increasing neutrophil protein on the bacterial envelope.

The killing of gram-negative bacteria by the bactericidal/permeability-increasing protein ( BPI ) of neutrophils requires surface binding, and is accompanied by a discrete increase in outer membrane permeability to small hydrophobic substances. This outer membrane alteration appears to be related to perturbation of outer membrane lipopolysaccharides (LPS). BPI causes extracellular release of LPS, but only at supra-saturating doses. Nevertheless, because the organization of LPS in the outer membrane is altered by pretreatment of bacteria with saturating doses of BPI (producing maximal bactericidal and permeability-increasing effects), the amount of LPS released during Tris-EDTA treatment is reduced by 80%. BPI markedly (approximately 50%) and selectively stimulates biosynthesis of LPS, suggesting an attempt by BPI -killed bacteria to repair outer membrane damage. The removal of surface-bound BPI by 40 mM Mg2+ initiates time- and temperature-dependent repair of the outer membrane permeability barrier and a further increase (approximately 170% of control) in LPS synthesis, even though the bacteria are no longer viable. Mg2+-induced repair is blocked when: 1) a temperature-sensitive mutant (Salmonella typhimurium HD50 ) with a conditional defect in LPS synthesis is incubated at the nonpermissive temperature (42 degrees C); and 2) LPS synthesis is selectively inhibited by a diazaborine derivative (Sandoz drug No. 84474). In contrast, repair is normal by the mutant at permissive temperatures (30 degrees C) and by the parent strain (S. typhimurium AG701 ) at both 30 degrees C and 42 degrees C. Inhibition (greater than 85%) of protein synthesis by chloramphenicol has little or no effect on repair. These findings indicate that the repair of the permeability barrier after the removal of BPI from the surface requires newly made LPS, but apparently no biosynthesis of other outer membrane constituents, which strongly suggests that the effects of BPI on LPS are mainly responsible for the break-down of the outer membrane permeability barrier.

Animals↗