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PubMed1998

Chemical processing in the coma as the source of cometary HNC.

The discovery of hydrogen isocyanide (HNC) in comet Hyakutake with an abundance (relative to hydrogen cyanide, HCN) similar to that seen in dense interstellar clouds raised the possibility that these molecules might be surviving interstellar material. The preservation of material from the Sun's parent molecular cloud would provide important constraints on the processes that took place in the protostellar nebula. But another possibility is that HNC is produced by photochemical processes in the coma, which means that its abundance could not be used as a direct constraint on conditions in the early Solar System. Here we show that the HNC/HCN ratio determined for comet Hale-Bopp varied with heliocentric distance in a way that matches the predictions of models of gas-phase chemical production of HNC in the coma, but cannot be explained if the HNC molecules were coming from the comet's nucleus. We conclude that HNC forms mainly by chemical reactions in the coma, and that such reactions need to be considered when attempting to deduce the composition of the nucleus from observations of the coma.

Cyanates↗

PubMed2000

The Coma Morphology Due to an Extended Active Region and the Implications for the Spin State of Comet Hale-Bopp.

We show that the circular character of continuum structures observed in the coma of comet Hale-Bopp around the perihelion passage is most likely due to a dust jet from a large extended active region on the surface. The coma morphology due to a wide jet is different from that due to a narrow jet. The latter shows foreshortening effects due to observing geometry; a wider jet produces more circular features. This circularization effect provides a self-consistent explanation for the evolution of near-perihelion coma morphology. No changes in the direction of the rotational angular momentum vector are required during this period, in contrast to the models of Schleicher et al. This circularization effect also enables us to produce near-circular coma features in the southeast quadrant in late February of 1997, and therefore it puts into question the basic premise on which Sekanina bases his morphological arguments for a gravitationally bound satellite nucleus.

Journal Article↗

PubMed2005

Conservation of genes and processes controlled by the quorum response in bacteria: characterization of genes controlled by the quorum-sensing transcription factor ComA in Bacillus subtilis.

Quorum or diffusion responses in bacteria are mediated by secreted signalling molecules that accumulate extracellularly as cultures grow to high density. The regulatory response to these signalling molecules can result in dramatic changes in gene expression. In Bacillus subtilis, a quorum response is mediated by a secreted 10-amino-acid modified peptide (ComX pheromone) that activates a receptor histidine kinase (ComP) that activates a response regulator transcription factor (ComA). We have used DNA microarrays to identify genes controlled by the ComX-ComP-ComA quorum-sensing pathway. We found that ComX, ComP and ComA affect the same set of genes, indicating that the kinase ComP is the only receptor for the signalling molecule ComX, and that ComA is the only transcription factor activated directly by ComP, under the conditions tested. Expression of over 20 genes appears to be controlled directly by this signalling pathway, and expression of over 150 additional genes, including those involved in competence development, appears to be controlled indirectly. The genes affected appear to have three general functions: (i) to co-ordinate physiological changes involved in developmental pathways, (ii) to produce extracellular products under conditions in which high concentrations of product are needed to be effective and (iii) to enhance survival, growth and colonization under conditions of crowding or limited diffusion. Many of the genes and processes controlled by the quorum response in B. subtilis are also regulated by quorum sensing in Gram-positive and Gram-negative bacteria. The quorum-sensing signalling molecules and regulatory proteins are quite different between Gram-positives and Gram-negatives and the convergent physiological regulation of similar genes and processes indicate the important and conserved nature of the quorum response.

Arginine↗

PubMed1989

Cloning and characterization of the regulatory Bacillus subtilis competence genes comA and comB.

comA and comB are Bacillus subtilis competence genes that are identified by insertions of Tn917lac. They are classified as early genes because of their expression throughout growth; the expression of late com genes increases sharply during the transition to the stationary phase. The comA and comB determinants were cloned, and the 5' and 3' termini of their transcripts were localized by low-resolution S1 nuclease protection experiments. comA and comB were found by Southern blotting to be localized near one another, but they were nevertheless apparently transcribed independently. Epistatic relationships among the com genes were explored by using the beta-galactosidase expressed from transcriptional fusions as a marker. Late com genes were found to be dependent on the products of comA, comB, and sin for their expression. The sin gene is a transcriptional regulator that is required for the development of competence (N. K. Gaur, E. Dubnau, and I. Smith, J. Bacteriol. 168:860-869, 1986).

Bacillus subtilis↗

PubMed1991

Genetic transformation in Streptococcus pneumoniae: nucleotide sequence analysis shows comA, a gene required for competence induction, to be a member of the bacterial ATP-dependent transport protein family.

The complete nucleotide sequence of comA, a gene required for induction of competence for genetic transformation in Streptococcus pneumoniae, was determined by using plasmid DNA templates and synthetic oligonucleotide primers. The sequence contained a single large open reading frame, ORF1, of 2,151 bp. ORF1 was included within the comAB locus previously mapped genetically and accounted for 50% of its extent. The predicted molecular weight of the largest polypeptide encoded within ORF1, 80,290, coincided with that measured previously (77,000) for the product of in vitro transcription-translation of the cloned comA locus. A Shine-Dalgarno sequence (AAAGGAG, delta G = -14 kcal) lay immediately upstream of ORF1. A sequence (TTtAat-17 bp-TAaAAT) similar to the Escherichia coli sigma 70 promoter consensus was located 410 bp upstream of ORF1. The deduced protein sequence of ComA showed a very strong similarity to the E. coli hemolysin secretion protein, HlyB, and strong similarities to other members of the family of ATP-dependent transport proteins, including the mammalian multidrug resistance P-glycoprotein. These similarities suggest that ComA functions in the transport of some molecule, possibly pneumococcal competence factor itself.

Adenosine Triphosphate↗

PubMed1991

DegS-DegU and ComP-ComA modulator-effector pairs control expression of the Bacillus subtilis pleiotropic regulatory gene degQ.

Production of a class of both secreted and intracellular degradative enzymes in Bacillus subtilis is regulated at the transcriptional level by a signal transduction pathway which includes the DegS-DegU two-component system and at least two additional regulatory genes, degQ and degR, encoding polypeptides of 46 and 60 amino acids, respectively. Expression of degQ was shown to be controlled by DegS-DegU. This expression is decreased in the presence of glucose and increased under any of the following conditions: growth with poor carbon sources, amino acid deprivation, phosphate starvation, and growth in the presence of decoyinine, a specific inhibitor of GMP synthetase. In addition, expression of degQ is shown to be positively regulated by the ComP-ComA two-component system. Separate targets for regulation of degQ gene expression by DegS-DegU and ComP-ComA were located by deletion analysis between positions -393 and -186 and between positions -78 and -40, respectively. Regulation of degQ expression by amino acid deprivation was shown to be dependent upon ComA. Regulation by phosphate starvation, catabolite repression, and decoyinine was independent of the two-component systems and shown to involve sequences downstream from position -78. The ComP-ComA and DegS-DegU two-component systems seem to be closely related, sharing several target genes in common, such as late competence genes, as well as the degQ regulatory gene. Sequence analysis of the degQ region revealed the beginning of an open reading frame directly downstream from degQ. Disruption of this gene, designated comQ, suggests that it also controls expression of degQ and is required for development of genetic competence.

Adenosine↗

PubMed1989

Prognosis after the first episode of gastrointestinal bleeding or coma in cirrhosis. Survival and prognostic factors.

Hepatic encephalopathy and gastrointestinal (GI) bleeding are the most serious complications in cirrhosis. The purpose of this study was to examine survival after the first episode of GI bleeding or coma, or both, and to identify variables associated with the subsequent survival in 284 consecutive patients with cirrhosis admitted to one division of hepatology over a period of 81 months. Patients who only bled had markedly longer survival than those who only had coma, whereas those who had both bleeding and coma had by far the poorest survival, only 15% being alive 1 year later. Several other variables showed a significant association with survival. In a Cox multiple regression analysis the following four variables showed significant association with a short survival: coma and bleeding at the episode, ascites, low prothrombin index, and high serum creatinine. The prognostic index derived from the Cox model, which was validated by a split-sample testing technique, may be used to refine prognostic estimation in this subgroup of severely ill cirrhotic patients.

Adult↗

PubMed1991

Fractional excretion of beta-2-microglobulin in the urine of patients with normal or reduced renal function and hepatic coma.

The purpose of this prospective study was to evaluate beta-2-microglobulin (beta 2m) as a differential diagnostic indicator between hepatic nephropathy (HN) and acute tubulointerstitial nephropathy (ATIN) in patients with reduced renal function and hepatic coma, and to determine whether beta 2m excretion could be used as a marker of renal impairment before increased serum creatinine (S-Cr) concentration or decreased creatinine clearance (Cr-Cl). Finally, the use of beta 2m as a prognostic indicator was investigated. Eighteen patients in hepatic coma grade III-IV were entered in the study and were divided into two groups in accordance with their renal function (serum creatinine above/below 180 mumol/l). The fractional excretion of beta 2m (FE-beta 2m) was used to monitor beta 2m elimination. The study failed to show any distinction in FE-beta 2m between HN and ATIN patients, presumably owing to the small number of patients. FE-beta 2m could not predict the development of renal failure earlier than the increase in S-Cr or decrease in Cr-Cl. However, a few patients who survived paracetamol intoxication had increased FE-beta 2M in the beginning of the coma and normal S-Cr and Cr-Cl. Patients who died as a result of paracetamol intoxication had both abnormal FE-beta 2m and abnormal S-Cr and Cr-Cl, suggesting that if therapy had been initiated earlier, when only FE-beta 2m was affected, these patients might have survived. All patients who survived, except three paracetamol- and one aminoglycoside-intoxicated patient, had normal FE-beta 2m in the beginning of the coma.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗

PubMed1976

[Therapeutic effect in 3 cases of hepatic coma in viral hepatitis].

The author reports his observation on three cases of coma hepaticum in viral hepatitis treated at the Internal Diseases Ward, Military Hospital, in the town of Asmara, Ethiopia. Parallelly with the usual hepatoprotective drugs and antibiotics, corticosteroids were administered as well as the preparation Reducdyn, containing homocysteine and cysteine-carriers of sulphhydryl groups. Complete restoration to health was achieved in two of the patients after three days in grave coma. The third patient was aroused from the comatose state for six hours but later had a lethal end on the eighth day post coma onset. According to the author, the combination of that preparation with corticosteroids is pathogenetically grounded and enables the administration of the latter in lower and safe doses. The author stresses upon the importance of early therapy in coma hepaticum.

Adult↗

PubMed1976

[Treatment of hepatic coma using extracorporeal perfusion with baboon and human liver as well as with activated charcoal].

In the 6 patients with hepatic coma hemoperfusions with 8 baboon and 2 human livers were carried out. Four awoke from the coma, one women could be discharged, but the others died of various complications and liver insufficiency. In the 4 patients with hepatic coma, 11 hemoperfusions with activated charcoal columns were performed. Two awoke from the coma, but they died of liver insufficiency. We were able to detect the elevation of preforming antibodies in a discharged patient.

Acute Disease↗

PubMedDate not supplied

[Plasmapheresis in the treatment of hepatic coma complicating viral hepatitis].

Therapeutic plasmaphereses using CS 3000 Fenwal Cell Separator were performed in 4 women and 2 men, aged between 17 and 44 years, with hepatic coma complicating acute viral hepatitis type B. One to four plasma exchanges per patient were performed, usually at the volume of 3000 ml per procedure. Two patients at II and IVa period of the coma, according to Aboun classification, survived. Four patients at II, III and two at III/IV period of the coma died. The authors suggest that in some cases exchange of large volumes of plasma in the treatment of hepatic coma complicating acute viral hepatitis may be a lifesaving procedure.

Acute Disease↗

PubMed1978

Tryptophan in hepatic coma.

The concentrations of tryptophan in serum and CSF, as well as that of 5-HIAA in CSF were investigated in various group of patients. Those with hepatic cirrhosis have normal total serum tryptophan. However, because of the low concentration of serum albumin the percentage of nonalbumin-bound tryptophan is elevated about 50 percent above the mean control value. By contrast tryptophan in the CSF was increased by 50 to over 800 percent. This suggests that there is also an increase in brain tryptophan and serotonin in the cirrhotic patients. No significant difference was found for the concentrations of tryptophan in CSF of patients in coma and those not in coma. Patients with hepatic coma had an elevated concentration of 5-HIAA in the lumbar CSF which may reflect the increase in this compound and in serotonin reported by Jellinger and Riederer (1977). However, following treatment with probenecid in order to block the egress of 5-HIAA from the CSF, the concentration of 5-HIAA in relation to that of probenecid was not significantly different for the group with hepatic coma as compared with the control group.

Hepatic Encephalopathy↗

PubMed1977

[Hepatic coma in liver cirrhosis. Prevention and treatment].

The prognosis of hepatic coma is poor if the patient has jaundice, ascites, defects in clotting factors, a low serum-albumin level and haemorrhage from oesophageal varices. After 5 years, the survival rate is less than 20%. Approved methods of intensive care are recommended. Cerebral oedema, respiratory and renal failure, infection and lactate acidosis are dangerous complications with the necessity to early treatment. The difficulty of parenteral nutrition depends on the extent of liver cell failure. In spite of the rise in blood ammonia mixtures of selected amino acids should be given in small doses. In selected cases temporary hepatic support and detoxification methods are indicated in hepatic coma. Charcoal haemoperfusion decreases the depth of coma and regulates the electroencephalogram, some patients fully recover consciousness. But there is no long-term improvement of survival-rates in cases complicated by bleeding oesophageal varices and by septic circulatory failure. The lethality of the first bleeding from varices is about 50%. Diagnostic endoscopy is necessary, sclerosing of oesophageal varicosis and laser-coagulation can be life-saving in hepatic pre-coma. The mortality of surgical procedures is more than 60%. Emergency anastomosis shunting portal blood has a better prognosis than ligation of the varices or oesophageal and high gastric transsection operations, demonstrated by surgical management in 248 cases. Even with this long-term succes is unusual.

Amino Acids↗

PubMed1983

[Hepatic coma. Principles of pathogenesis and treatment. 2: Treatment, prognosis].

According to the multifactorial pathogenesis of hepatic coma, generally caused by the increased formation of toxic protein metabolites in the gut, the most important therapeutical measure is the cleaning and acidifying of the gut. This is possible very simply and cheaply by high enemas of sodium acetate buffers of pH 4,5 and lactulose. If necessary, neomycin or paromomycin must be administered in high doses of 6--8 gm/daily to reduce the pathogenic intestinal bacteria. The detoxification capacity of liver and brain can be improved by intravenous and later oral administration of ammonia reducing amino acids such as arginine, ornithine, and aspartic acid (10--20 gm/daily). They diminish also the elevated serum phenols. Very helpful are also branched chain amino acids which improve apparently the detoxification capacity of the muscle. Very important is the normalization of disturbances of the water and electrolyte balance, especially the normalization of hypokalemia. Very difficult is a successful treatment of cerebral edema and the disturbances of blood coagulation. In special cases of endogenous hepatic coma liver perfusions, hemodialysis, charcoal perfusions a.s.o. can eliminate successfully toxic protein metabolites, whilst this treatment is generally insufficient in the more frequent exogenous hepatic coma. In summary the prognosis of hepatic coma is also nowadays very serious and can only be improved by the early recognition and elimination of exacerbating factors.

Combined Modality Therapy↗

PubMed1984

Visual evoked potentials in a rabbit model of hepatic encephalopathy. I. Sequential changes and comparisons with drug-induced comas.

The recording of visual evoked potentials in rabbits has been shown to be an objective, reproducible, noninvasive technique for quantitating changes in the pattern of cerebral neuronal activity. The development of hepatic encephalopathy due to galactosamine-induced fulminant hepatic failure was consistently associated with a series of distinctive changes in the visual evoked potential waveform. The pattern of the visual evoked potential in hepatic coma (due to galactosamine-induced fulminant hepatic failure) differed fundamentally from that in ether-induced coma, but was identical to that in comas induced by three drugs which activate gamma-aminobutyric acid-ergic neural mechanisms: pentobarbital, diazepam, and muscimol. These findings are compatible with activation of the gamma-aminobutyric acid inhibitory neurotransmitter system contributing to cerebral neuronal inhibition in hepatic coma due to galactosamine-induced fulminant hepatic failure.

Animals↗

PubMed1997

Hepatic coma recovered after interventional obliteration for ileocecal-inferior vena cava shunt--report of one case.

We performed interventional angiography (IVA) in a patient with liver cirrhosis (LC) and hepatoma (HCC) who experienced repeated attacks of unconsciousness due to hyperammonemia caused by ileocecal-inferior vena cava (IC-IVC) shunt and succeeded in the treatment. We report the results below. The patient, 53-year-old male, underwent endoscopic injection sclerotherapy for esophageal varix due to LC followed by splenectomy for pancytopenia in 1986. He made good progress. However intraarterial anticancer therapy was conducted for HCC in 1994. From that time hepatic coma began to appear and its frequency gradually increased. Hepatic coma occurred once every 3 weeks from June 1996. He was thus admitted to our hospital. Hematobiochemical testes showed that ammonia level was 297 mcg/dl. Albumin 2.8d/dl, and Total-Bilirubin 10.78 mg/dl. Arterioportography from superior mesenteric artery showed most of portal blood flowed away from the liver though the ileocolic vein to IVC. We decided to conduct IVA for treatment. Specially, a 6Fr balloon catheter was inserted from the right inguinal region into a shunt to the portal vein though IVC by the Seldinger technique. The balloon was inflated in the shunt to close the shunt. Six ml of 5% ethanolamime oleate with iopamidol was injected because retrograde angiography showed that iopamidol was flowed out via testicular vein to IVC. The balloon catheter was retained for 24 hours. Angiography, conducted from the catheter again 24 hours later, showed that the shunt was occluded, blood ammonia level was 71 mcg/dl after occlusion. Hepatic coma was not observed after treatment. We encountered a very rare case who repeated hepatic comas due to IC-IVC shunt and recovered dramatically after IVA.

Angiography↗

PubMed1997

Does modification of the Innsbruck and the Glasgow Coma Scales improve their ability to predict functional outcome?

BACKGROUND: The accurate prediction of functional outcome requires the development of multivariate models. To enhance their contribution to such models, the predictive power of each component must be optimized. OBJECTIVES: To improve the predictive power of coma scales as the first step in building more sophisticated multivariate models to predict specific levels of functional outcome. DESIGN: Prospective descriptive study. SETTING: Neurology and neurosurgery intensive care unit (NNICU) in a tertiary care academic center. PATIENTS: Eighty-four patients with acute traumatic brain injury, intracerebral hemorrhage, subarachnoid hemorrhage, or ischemic stroke. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The Glasgow Coma Scale (GCS) and Innsbruck Coma Scale (ICS) were administered within 24 hours of admission to the NNICU and then at 48-hour intervals until discharge of the patient from the NNICU. The assessments were performed by 3 occupational therapy graduate students working under the supervision of the medical director of the NNICU. The functional outcome at 3 months after discharge from the hospital was assessed by telephone by the same nurse using the following categories: (1) dead, (2) receiving nursing home or custodial care, (3) home with help, or (4) independent. Cronbach's alpha estimates of reliability for each scale were computed using all scores obtained during the study. The analyses indicated that the verbal response item of the GCS and the oral automatisms item of the ICS were less reliable in this patient population. The scales were modified by deleting those items, and predictive validity for the original and modified scales was computed using a discriminant function of the admission scores. RESULTS: Before modification, both scales were best at predicting independence (GCS and ICS, 71% correct) and mortality (GCS, 60% correct; ICS, 56% correct). The modifications produced a modest improvement in the ability of both scales to better predict levels of outcome (modified GCS: home with help, 33% correct, independent, 71% correct; modified ICS: home with help, 0% correct, independent, 74% correct). CONCLUSIONS: By deleting items with low reliability from the ICS and the GCS we achieved improved reliability and predictive validity. The improvement in predictive power, however, was inadequate to accurately predict functional outcome. Combining clinical scales with other demographic, physiological, functional, and radiographic data will be needed to achieve useful predictions of functional outcome.

Adult↗

PubMed2005

Early clinical predictive factors during coma recovery.

In severe brain injury patients few studies have examined the role of early clinical factors emerging before recovery of consciousness. Patients suffering from vegetative state and minimally conscious state in fact may need variable periods of time for recovery of the ability to follow commands. In a previous study we retrospectively examined a population of very severe traumatic brain injury patients with coma duration of at least 15 days (prolonged coma), and we found, as significant predictive factors for the final outcome, the time interval from brain injury to the recovery of the following clinical variables: optical fixation, spontaneous motor activity and first safe oral feeding. Psychomotor agitation and bulimia during coma recovery were also favourable prognostic factors for the final outcome. In a further study, also as for the neuropsychological recovery, the clinical variable with the best significant predictive value was the interval from head trauma to the recovery of safe oral feeding. In the present study the presence of psychomotor agitation diagnosed by means of LCF (score 4 = confused-agitated) at the admission time in rehabilitation predicted a statistically significant better outcome at the discharge time in comparison with patients without agitation.

Coma, Post-Head Injury↗