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PubMed1986

Effect of age on the solubility of volatile anesthetics in human tissues.

To determine the effect of age on the solubility of volatile anesthetics in human tissues, the authors measured the solubilities of isoflurane, enflurane, halothane, and methoxyflurane in vitro at 37 degrees C in 35 postmortem human tissue specimens. Specimens were taken from neonates, and young (20-50 yr), middle-aged (50-70 yr), and elderly adults (greater than 70 yr). Brain/gas, heart/gas, and liver/gas partition coefficients for all four anesthetics increased significantly (P less than 0.05) between birth and adulthood, although brain/gas partition coefficients in young adults tended to be higher than those in middle-aged and elderly adults. Heart/gas and liver/gas partition coefficients tended to increase with aging. Muscle/gas partition coefficients for the four anesthetics increased linearly with age. Fat/gas partition coefficients did not change significantly with age. Tissue/blood solubilities for the four anesthetics were of the same order of magnitude for a given tissue and age group. Tissue/blood solubilities for enflurane were 30% lower than those for isoflurane in the same tissue and age group. In summary: the solubility of volatile anesthetics in human tissues increases with age; the lower solubility of anesthetics in neonates partially explains the more rapid increase of alveolar and tissue anesthetic partial pressures in neonates; despite the higher blood solubility of enflurane, its lower tissue solubility may explain a rate of recovery comparable with that of isoflurane.

Adipose Tissue↗

PubMed1983

Lipid solubility is correlated with hypnotic and hypothermic responses of long-sleep (LS) and short-sleep (SS) mice to various depressant drugs.

The long-sleep (LS) and short-sleep (SS) lines of mice have been selected for a difference in duration of ethanol-induced sleep time. In our previous study, recent generations of the two lines were found to exhibit differential hypnotic and hypothermic responses to pentobarbital which appear to be explained by differences in elimination. Casual observation that the LS mice were fatter than the SS suggested that this discrepancy may influence the responses of these animals to sedative-hypnotic drugs which differ in lipid solubility. The present study was designed to determine whether the LS and SS mice differ in hypnotic and hypothermic responses to two barbiturates which differ in lipid solubility; to the highly lipid soluble tertiary alcohol, ethchlorvynol; and to the water soluble depressant, methyprylon. Mice of the SS line were more responsive to the lipid soluble depressants than were LS mice, and increasing the lipid solubility of the barbiturates resulted in a greater difference between the lines. LS mice were more responsive to the water soluble depressant, apparently due to differential central nervous system sensitivity rather than to differences in elimination. The whole-body lipid content of the LS mice is double that of the SS mice. The influence of body lipid content on drug disposition may accentuate the elimination differences that result in the lesser responsivity of LS mice to barbiturates and possibly ethchlorvynol. This study indicates that sedative-hypnotic drugs of varying lipid solubilities may not share common mechanisms of action.

Animals↗

PubMed1980

Solubility of inert gases in biological fluids and tissues: a review.

Data have been tabulated from more than 150 references on the solubility of inert gases in fluids and tissues of biological interest. Thirty-two gases have been studied in blood with measured solubility ranging from 0.005 to 16 ml of gas at 37 degrees C per ml of blood per ATA (Ostwald coefficient). For most gases, solubility in other tissues such as muscle or brain is between 60% and 300% of blood solubility. Measured solubilities in biological tissues do not correspond well to solubility in water and oil. Most gases decrease in solubility by 1%-6% for each degree C rise in temperature. The effect of pressure on solubility has not been well studied, and only crude estimates can be obtained by using methods of chemical thermodynamics.

Humans↗

PubMed1995

Blocking measles virus infection with a recombinant soluble form of, or monoclonal antibodies against, membrane cofactor protein of complement (CD46).

Human membrane cofactor protein (MCP, CD46) functions as an inhibitor of the complement (C) cascade to protect host cells from C attack, and as a receptor for measles virus (MV). Normal human sera contains 10-60 ng/ml of naturally produced soluble forms of MCP, which is also a cofactor for the factor I-mediated inactivation of C3b. We produced monoclonal antibodies (mAb) against MCP and a recombinant soluble form of MCP similar to the natural soluble forms, and tested their ability to block MV infection. Vero cells and CHO cells expressing human MCP were the targets. Of the antibodies tested, M75 and M177, which blocked the C regulatory activity of MCP, efficiently blocked MV infection. More than 50 micrograms/ml of the soluble form moderately blocked MV infection of CHO cells expressing MCP, but barely blocked that of Vero cells. The two mAb and the soluble form also inhibited MV H protein-mediated green monkey erythrocyte rosette formation. A quantitative analysis suggested that 30 micrograms/ml of the soluble form functionally corresponded to 0.2 microgram/ml of M177 or M75. These data established that the C regulatory function and the MV receptor function of MCP were blocked simultaneously by the individual mAb, and that soluble forms of MCP could inhibit MV infection in cells expressing human MCP, although doses far higher than the natural concentration of soluble MCP were required.

Animals↗

PubMed1993

[The solubility of drugs in lipoid vehicles].

A method for determination of drug substances solubility in lipophilic solvents is presented. The solubility was determined in lipophilic suppository bases meltings, in pharmaceutical lipoids as Oleum Ricini, Oleum Arachidis, Cera perliquida, Paraffinum perliquidum and in chemically defined lipoids as n-hexadecane, 1-hexadecane, cetylic alcohol, palmitic acid, cetylpalmitate. Consequences from chemical constitution of substances for solubility are discussed, also consequences from chemical constitution and dielectric constants of lipoidic solvents for their solution behavior. For the substances investigated, the apparent partition coefficients in the two-phase systems lipoid/phosphate buffer pH 7,4 and n-octanol/phosphate buffer pH 7,4 were determined, also the solubility in phosphate buffer. The results show, that connections between partition coefficients and solubility in lipophilic or aqueous phases do not exist. On the other hand, an indirect proportionality between water solubility and lipoid solubility also does not exist. In consequence, interpretations of drug release from lipophilic systems have to be proceeded from exact knowledge of partition behavior and solubilities in both the lipophilic and aqueous phase.

Chemistry, Pharmaceutical↗

PubMed1995

Evaluation of a soluble fibrin assay in patients with suspected deep vein thrombosis.

BACKGROUND: The objective of this study was to determine the clinical utility of an enzyme immunoassay (EIA) for soluble fibrin in patients with clinically suspected deep vein thrombosis (DVT). METHODS AND RESULTS: 101 unselected patients with clinically suspected DVT underwent blood sampling for measurement of plasma levels of soluble fibrin, and objective testing for DVT. According to results of the objective tests, patients were classified as DVT-positive (n = 34) or DVT-negative (n = 67). Using different cut-points of soluble fibrin results, the sensitivities, specificities, positive and negative predictive values of the soluble fibrin assay were calculated. A soluble fibrin result of < or = 0.75 mg/ml showed a sensitivity and negative predictive value of 100%, and a specificity of 17.9% for DVT, a soluble fibrin result of < or = 1.40 mg/ml showed a sensitivity of 91.2% and a negative predictive value of 93.6%, and a specificity of 65.7% for DVT, whereas a soluble fibrin result of < or = 8.0 mg/ml showed a specificity and positive predictive value of 100% for DVT. CONCLUSIONS: This study demonstrates that the soluble fibrin assay used in the study has potential clinical utility as a diagnostic test in patients with clinically suspected DVT and supports further evaluation of this assay.

Evaluation Studies as Topic↗

PubMed1996

Soluble intercellular adhesion molecule-1 in colorectal cancer and its relationship to acute phase proteins.

Increased concentrations of soluble intercellular adhesion molecule-I (ICAM-1) have been reported in a number of diseases including cancer. This study was undertaken to evaluate soluble ICAM-1 in colorectal cancer and its relationship to an unspecific acute phase response. Fifty six patients (25 with advanced colorectal cancer and 31 out-patients after radical surgical treatment) were included. Soluble ICAM-1 was measured by enzyme immunoassay. Four acute phase proteins (C-reactive protein, acid alpha 1-glycoprotein, haptoglobin and ceruloplasmin) were estimated by immuno-nephelometry. No significant increase of soluble ICAM-1 could be demonstrated in the patients compared to a control group (median 273 ng/ml vs. 270 ng/ml). Furthermore, patients with advanced colorectal cancer did not demonstrate elevated soluble ICAM-1 compared to follow-up out-patients. Patients with present acute phase response as determined by C-reactive protein were shown to have increased soluble ICAM-1 compared to patients without acute phase reaction. Using other acute phase proteins no difference for soluble ICAM-1 has been shown. Our data suggest an association between acute phase response and increased ICAM-1 in patients with colorectal cancer which should be considered when the diagnostic and/or prognostic usefulness of soluble ICAM-1 is to be evaluated.

Acute-Phase Proteins↗

PubMed1994

Soluble complement receptor type 1 (CD35) is released from leukocytes by surface cleavage.

The soluble form of complement receptor type 1 in human plasma (sCR1) might correspond to the shedding of the receptor by proteolytic cleavage at the cell surface. A new enzyme-linked immunosorbent assay (ELISA) was established to specifically measure membrane-bound CR1 using a rabbit polyclonal antibody against a 19-amino acid peptide corresponding to the C-terminal sequence of the intracellular domain of CR1 (mCR1-ELISA). This ELISA measured CR1 from solubilized erythrocyte membranes, polymorphonuclear leukocytes (PMN), a B lymphocyte cell line and renal podocyte-derived urinary vesicles in a dose-dependent manner. In contrast, and similarly to recombinant soluble CR1 which lacks the intracellular domain of CR1, plasmatic sCR1 was not recognized, suggesting that sCR1 corresponds to an extracellular fragment of whole CR1. In vitro, PMN were shown to release a soluble form of CR1 which was also not recognized in the mCR1-ELISA, and whose size was smaller (5 kDa) than the CR1 of PMN cell membranes. The release of soluble CR1 was highest for PMN and HL60 cells, followed by U937 cells and three different B lymphocyte cell lines, whereas T lymphocyte cell lines did not release soluble CR1. The levels of CR1 gene expression were also higher in PMN compared to remaining blood leukocytes and the different cell lines tested above. Incubation of PMN with formyl-methionyl-leucyl-phenylalanine, tumor necrosis factor-alpha or lipopolysaccharide accelerated the release of soluble CR1, and incubation with granulocyte/macrophage colony-stimulating factor resulted in sustained CR1 gene expression and higher total soluble CR1 release. Our results suggest that soluble CR1 is produced by cleavage of cell surface CR1, and that a large fraction of human plasma sCR1 is cleaved from PMN. The release of sCR1 by leukocytes may play a role in the control of complement activation at sites of inflammation.

Amino Acid Sequence↗

PubMed1992

High concentrations of soluble tumor necrosis factor receptors in ascites.

Ascites and plasma concentrations of soluble tumor necrosis factor receptors p55 and p75 were measured in a prospective study in 34 patients (35 occasions of ascites) with hepatic (5 infected and 21 uninfected) and malignancy-related (9) ascites. All patients had high concentrations of both soluble tumor necrosis factor receptors in ascites and plasma; these were about 500 times higher than the corresponding tumor necrosis factor-alpha concentrations. Ascites levels of soluble tumor necrosis factor receptors p55 and soluble tumor necrosis factor receptors p75 were significantly elevated in patients with malignancy-related (p55: 26.0 +/- 8.6 ng/ml; p75: 20.5 +/- 17.4 ng/ml; mean +/- S.D.) and infected ascites (p55: 25.1 +/- 10.9 ng/ml, p75: 22.6 +/- 11.0 ng/ml) compared with patients with uncomplicated hepatic ascites (p55: 10.1 +/- 4.4 ng/ml; p75: 6.0 +/- 2.6 ng/ml). Patients with infected or malignancy-related ascites also showed higher soluble tumor necrosis factor receptor concentrations in plasma than did patients with plain hepatic ascites. Successful antibiotic treatment of peritonitis reduced soluble tumor necrosis factor receptor p55 and p75 ascites levels in three patients from 24.2 +/- 15.2 ng/ml to 10.7 +/- 1.9 ng/ml and from 20.2 +/- 14.4 ng/ml to 7.5 +/- 1.8 ng/ml, respectively. Soluble tumor necrosis factor receptors p55 and p75 at cutoff levels of 16.5 ng/ml and 9.5 ng/ml, respectively, differentiated between infected or malignant and plain hepatic ascites with diagnostic accuracies of 94% and 89%, respectively. They did not differentiate between infected and malignant ascites. The concentrations of soluble tumor necrosis factor receptor p55 were usually higher in ascites than in plasma in all subgroups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1979

Comparative tumor-inhibitory and anti-bacterial activity of soluble and particulate glucan.

A soluble fraction of particulate glucan was prepared and evaluated for its anti-tumor and anti-bacterial activity. Thin-layer chromatographic analysis indicated that the soluble preparation was composed of a variety of polyglucoses. Intravenous administration of soluble or particulate glucan resulted in significant reductions in the growth of a syngeneic anaplastic mammary carcinoma and melanoma B16. Survival data demonstrated that intravenous administration of soluble or particulate glucan prolonged survival of A/J and C57BL/6J mice with subcutaneous tumor implants. As regards to bacterial infections, soluble and particulate glucan decreased renal necrosis in S. aureus challenged mice as compared to control mice. Although the exact nature of the active soluble fraction(s) of glucan remains to be delineated, these studies demonstrate that a soluble glucan preparation exhibits significant anti-tumor and anti-staphylococcal activity. The active soluble fraction of particulate glucan may be preferable to particulate glucan in view of the inherent ease of parenteral administration.

Animals↗

PubMed1995

Induction of peripheral tolerance by intrathymic inoculation of soluble alloantigens: evidence for the role of host antigen-presenting cells and suppressor cell mechanism.

Intrathymic (IT) inoculation of soluble alloantigens (Ag) obtained from 3 M KCl extracts of resting T-cells induces donor-specific tolerance to cardiac allografts and islet allografts. This study examined the cellular basis of induction of transplantation tolerance by IT injection of soluble Ag. Our results show that while IT inoculation of 2 mg soluble donor Ag on Day -7 relative to Lewis islet transplantation induced specific unresponsiveness to islet allografts (> 200 days) in naive diabetic recipients, IT inoculation of 2 mg soluble Ag on the same day as islet transplantation did not prolong islet allograft survival in the same Lewis-to-WF rat combination. To define the role of donor APCs in intrathymic tolerance, we showed that IT injection of an admixture of 1 x 10(4) donor DC and 2 mg soluble Ag caused acute islet graft rejection. In contrast, addition of 1 x 10(4) recipient-type DC to the IT inoculum did not prevent long-term graft survival. This finding suggests that while the presence of donor APCs in the inoculum does not appear necessary for IT-alloantigen to induce peripheral tolerance, presentation of the soluble Ag in the thymus is dependent on host APCs. This conclusion is supported by our in vitro MLR experiments which showed that in vivo WF-Ag-primed Lewis T-cells proliferated specifically to WF-soluble Ag and that the response was enhanced 14-fold by the addition of responder-type DC. Addition of anti-Lewis MHC class II mAb specifically blocked the alloresponse, thus suggesting that in vivo Ag-primed T-cells are capable of recognizing and proliferating in response to allopeptides presented by responder APCs. We also showed that adoptive transfer of syngeneic naive T-cells into unresponsive recipients failed to break tolerance to long-term surviving islet allografts. This finding suggests that tolerance in this model is not due to a lack of T help. On the other hand, the adoptive transfer of spleen cells, but not sera, from the unresponsive WF recipients bearing long-term (> 120 days) functioning Lewis islets resulted in prolonged survival of donor-type but not third-party islet allografts in secondary syngeneic hosts. Our data suggest that the tolerogenic effect of IT inoculation of soluble Ag is dependent on the indirect pathway of Ag presentation and clonal deletion of alloreactive T-cells in the thymus, while suppressor/regulatory mechanism may be involved in the maintenance of peripheral tolerance.

Animals↗

PubMed1996

Soluble tumor necrosis factor receptors are present in human vitreous and shed by retinal pigment epithelial cells.

Tumor necrosis factor-alpha (TNF) has been implicated in the pathogenesis of several retinal diseases. Soluble forms of the TNF receptors, p55 (55 kDa) and p75 (75 kDa), have recently been identified in biological fluids and may regulate TNF activity. The potential biological significance of these receptors for the human retina was examined by determining their presence in human vitreous and their release from eye cup explants in which the retina has been removed leaving an intact retinal pigment epithelium (HRPE). Normal human vitreous and conditioned medium from eye-cup HRPE explants demonstrated the presence of soluble p55 and p75. Soluble p55 was significantly more abundant than p75 in all vitreous samples (P < 0.03). Conditioned medium from eye-cup HRPE explants contained significantly more soluble p55 than p75 (P < 0.00002). Enzyme-linked immunosorbent assay showed the presence of soluble p55, and not p75, in conditioned medium from primary cultured HRPE cells. Activation of the protein kinase C pathway in these cells with the phorbol ester PMA significantly increased the release of soluble p55 (P < or = 0.001); whereas, pharmacological inhibition of protein kinase C with calphostin-C significantly decreased the shedding of p55 (P < or = 0.001). The results indicate that primary cultured HRPE cells shed p55 and regulate this shedding in part through the protein kinase C pathway. The presence of soluble TNF receptors within normal human vitreous and within conditioned medium from the eye-cup HRPE explant model suggests that these soluble receptors may have a biological function in the eye.

Aged↗

PubMed1999

Observations on the Apparent Solubility of Carbonate-Apatites.

Previousreports indicating that the apparent solubilities of carbonate-apatites are low appear to conflict with findings that carbonate incorporation into the apatite structure tends to reduce stability. Carbonate-apatites were prepared by a precipitation method and by hydrolysis of monetite and brushite. Apparent solubility profiles were determined by measuring dissolution after exposure for 24 h to acetate buffers with known saturations with respect to hydroxyapatite. All preparations showed a range of apparent solubilities, in agreement with previous work. Precipitated samples had higher apparent solubilities than samples prepared by hydrolysis and this was correlated with differences in crystallinity. Further experiments showed that pyrophosphate ion reduced the apparent solubility, but it was concluded that pyrophosphate occurring naturally in synthetic apatites would be insufficient to cause low apparent solubilities. Microscopical observations showed that precipitated carbonate-apatites were composed of small crystals of uniform size, whereas carbonate-apatites prepared by hydrolysis consisted of both small crystals and very large crystals. The low apparent solubilities observed in the latter preparations are attributed to the large crystals. The surface phenomena possibly involved in apparent solubility behavior are discussed. Copyright 1999 Academic Press.

Journal Article↗

PubMed1997

Soluble leucocyte adhesion molecules in diabetic retinopathy stimulate retinal capillary endothelial cell migration.

Diabetic retinal neovascularisation is considered to be a consequence of retinal ischaemia caused by capillary occlusion. Capillary occlusion is the result of microvascular thrombi in which erythrocytes, platelets and leucocytes each may play a role. We investigated the role of leucocytes in this process and the subsequent angiogenic response. We studied the serum levels of the soluble leucocyte adhesion molecules soluble E-Selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) in the serum of 93 patients with insulin-dependent diabetes (IDDM) and varying degrees of retinopathy and 47 healthy age and sex matched control subjects. We also measured the ability of serum to stimulate retinal capillary endothelial cell migration using an assay of angiogenesis in vitro. Soluble E-Selectin and sVCAM-1 levels were raised in all patients with IDDM (p < 0.001; p < 0.001) particularly those with retinopathy (p < 0.001; p < 0.001). Soluble E-Selectin levels were highest in the patients with severe non-proliferative diabetic retinopathy (p < 0.001) and sVCAM-1 levels were highest in patients with proliferative diabetic retinopathy (p < 0.01). In contrast soluble ICAM-1 levels were the same in patients and control subjects (p > 0.05). Soluble E-Selectin levels in diabetic patients were correlated with the level of glycated haemoglobin (p < 0.05). Retinal endothelial cell migration-inducing (ECMI) activity was increased in patients with IDDM (p < 0.01) in particular in those with retinopathy (p < 0.01). Furthermore, in vitro ECMI activity could be blocked by antibodies to sVCAM-1 and sE-Selectin. These data point to a functional role for leucocyte adhesion in the microvasculopathy of diabetic retinopathy and may have implications for the induction of retinal angiogenesis.

Adult↗

PubMed1984

Karyophobic proteins. A category of abundant soluble proteins which accumulate in the cytoplasm.

The cytoplasm of oocytes of Xenopus laevis is enriched in several soluble proteins which are either absent from the nucleus or are present there at very low concentrations. These molecules, collectively referred to as karyophobic (from the Greek verbs and which are meant here in the sense of "to be afraid of" or "to avoid") proteins represent more than 20% of the total soluble cytoplasmic proteins and include some of the most abundant soluble cellular components. They may be recovered from high-speed supernatant (S-100) fractions and, following sucrose gradient centrifugation, most of them appear in the form of complexes smaller than 8.5 S. On denaturation in urea and two-dimensional gel electrophoresis these proteins appear to be comprised of polypeptides of widely different sizes (ca Mr 15 000-230 000) and isoelectric points covering a broad range of pH values (4.2-8.0). Gel filtration and isoelectric focusing of native karyophobic proteins show that the majority occur in acidic complexes smaller than Mr 150 000, including one case of a small karyophobic protein (C9; Mr 30 000). In contrast to karyophilic proteins and proteins equilibrating between nucleus and cytoplasm karyophobic soluble proteins from [35S]methionine-labelled ooplasms, when injected into unlabelled oocytes, remain in the cytoplasm. Human proteins with a similar karyophobic behaviour have been identified in fractions of soluble proteins from HeLa cells; there, the major karyophobic protein (HCa Mr 36 000) is also one of the most abundant soluble proteins. We conclude that the specific nucleocytoplasmic compartmentalization of soluble proteins is governed not only by the principles of exclusion of large molecules from nuclear uptake and the existence of karyophilic signals in certain proteins but that a series of soluble, globular proteins exist in the cytoplasm, which have other molecular features which selectively exclude them from distribution over the nucleus. The possible functional role of the selective enrichment of these abundant proteins, which so far have escaped attention, in establishing a cytoplasmic milieu is discussed.

Animals↗

PubMed1984

Effects of metals and organic compounds on hepatic glutathione, cysteine, and acid-soluble thiol levels in mullet (Mugil cephalus L.).

The hepatic acid-soluble thiol content of striped mullet (Mugil cephalus) exposed to cadmium (10 mg/liter seawater), mercury (200 micrograms/liter), fluorene (100 micrograms/liter), dibenzofuran (750 micrograms/liter), or a 20% water-soluble fraction of a No. 2 fuel oil, and of winter flounder (Pseudopleuronectes americanus) exposed to pentachlorophenol (200 micrograms/liter) for up to 3 weeks was determined. Exposure to these chemicals caused an elevation of hepatic acid-soluble thiol content over control values. Similarly, the acid-soluble thiol content was 1.75 times control values 24 hr after injection with acetaminophen (40 mg/100 g body wt, ip). In contrast, hepatic acid-soluble thiol concentrations did not fluctuate after feeding or during short-term starvation, or after acute or chronic physical trauma. Thus, the increase in hepatic acid-soluble thiols observed in mullet appears to be a specific response to chemical insult. The effect of chemical exposure on specific thiols can vary with the compound under investigation. Glutathione accounted for most of the acid-soluble thiol increase observed in mullet exposed to oil, whereas other acid-soluble thiols were also elevated after exposure to cadmium. Injection of [14C]glycine into cadmium- and oil-treated mullet showed that hepatic uptake of this amino acid substrate and its incorporation into hepatic glutathione increased after chemical exposure. The proportion of the total [14C]glycine in the liver incorporated into glutathione was unchanged after oil exposure, but was significantly increased in cadmium-exposed fish. These results suggest that chemicals may elevate glutathione content by enhancing the hepatic uptake of amino acid substrates and also the activity of biosynthetic enzymes.

Acetaminophen↗

PubMed1989

Serum levels of soluble Tac peptide in acute and chronic hepatitis B virus infection.

Serum-soluble Tac peptide was measured by an enzyme-linked immunosorbent assay in 12 patients with acute type B hepatitis, 33 patients with chronic type B hepatitis, and 15 age- and sex-matched controls. All 12 patients with acute type B hepatitis had elevated levels of soluble Tac peptide with a mean (+/- SD) of 1527 +/- 432 U/ml, significantly higher than that of normal controls (264 +/- 74 U/ml) or patients with chronic type B hepatitis (646 +/- 399 U/ml). Serial follow-up showed that serum levels of soluble Tac peptide tended to return to normal 2-4 months after onset of acute hepatitis along with the normalization of alanine aminotransferase and seroconversion of hepatitis B surface antigen (HBsAg) to anti-HBs. Patients with chronic type B hepatitis also had significantly higher levels of soluble Tac peptide than normal controls, although only 63.6% (21/33) of them had a level greater than the upper limit of normal. Serum levels of soluble Tac peptide in patients with chronic type B hepatitis varied considerably with the inflammatity in liver. The hepatitis B e antigen (HBeAg)-positive patients with chronic active liver disease had significantly higher levels of soluble Tac peptide (928 +/- 424 U/ml) than HBeAg-positive (412 +/- 146 U/ml) or anti-HBe-positive (424 +/- 175 U/ml) patients with chronic persistent hepatitis or minimal histological change. In addition, there was a significant positive correlation between serum levels of soluble Tac peptide and alanine aminotransferase. These findings suggested that activation of T cells might play an important role in the pathogenesis of acute and chronic type B hepatitis. Assay of serum-soluble Tac peptide might provide a simple and useful means to better understand the immune mechanisms of acute and chronic hepatitis B virus infection.

Adolescent↗

PubMed1983

Identification and purification of a protein involved in the activation of nitrate reductase in the soluble fraction of a chlA mutant of Escherichia coli K12.

The isolation and purification of a protein which is the presumed product of the chlA gene has been achieved. This protein, which we have named Protein PA, has been isolated from the soluble fraction of a chlB mutant. The protein was identified by its ability to activate nitrate reductase (EC.1.7.99.4) when mixed with a soluble fraction derived from a chlA mutant. The protein has a molecular weight of about 72 000 and is composed of a single polypeptide chain. Antiserum specific for Protein PA has been produced. Removal of Protein PA from the soluble fraction of chlB mutant by immunoprecipitation with this antiserum leads to the loss of the ability of the preparation to activate nitrate reductase when mixed with a soluble fraction from a chlA mutant. Protein PA, therefore, performs an essential but as yet undefined role in the activation process. Employing this antiserum Protein PA could be quantified by rocket immunoelectrophoretic analysis. The activity of the isolated Protein PA is low, since comparatively large amounts of Protein PA are required to activate the nitrate reductase present in the soluble fraction of the chlA mutant. The mixing of Protein PA with the chlA mutant soluble fraction leads to activation of nitrate reductase in both a soluble and a membranous form, as is the case when the complete soluble fraction of the chlB mutant is used in place of Protein PA. After activation, however, only a small proportion (15%) of the Protein PA is associated with the newly formed membranous material.

Bacterial Proteins↗