In screening a rat mucosa cDNA subtraction library, a clone that exhibited a remarkable degree of homology with a previously described cDNA from the green garden pea, designated the 26g pea turgor protein, was found. A partial cDNA sequence from rat and a complete cDNA sequence from human were obtained. The deduced human protein had a molecular weight of 55,285 and was designated antiquitin because of its remarkable level of conservation through evolution. Human antiquitin was 60% homologous to the green pea 26g with only a single amino acid gap in each sequence. The 66 amino acids at the carboxyl ends of the human antiquitin and pea 26g proteins were 86% identical, and one segment of 52 amino acids was 92% identical. A similar partial sequence encoding 164 amino acids has been detected in Caenorhabditis elegans. Yeast DNA was found to have sequences that hybridize with a human antiquitin probe on Southern blotting. Analysis of the amount of mRNA in various rat and human tissues indicated that the largest amounts were found in rat kidney and liver and in cultured human hepatoma cells. Only minimal amounts were detected in human peripheral blood leukocytes, rat lung, or cultured human fibroblasts. Attempts to induce the mRNA by heat-shock, dehydration, ionizing irradiation, or treatment with iron, t-butylhydroperoxide, or glucocorticoids were unsuccessful. The function of the protein remains unknown.

Aldehyde Dehydrogenase↗

PubMed1994

Sequence analysis of the proximal promoter region of the human alpha-fetoprotein gene in hepatocellular carcinoma.

We have examined whether or not mutations exist in the proximal promoter region of the human alpha-fetoprotein (AFP) gene in the hepatocellular carcinoma (HCC) tissue. Genomic DNA was extracted from four patients: one HCC tissue, one HCC and its corresponding non-cancerous (cirrhosis) tissues, one liver cirrhosis (LC) tissue without HCC and one matching HCC tissue and peripheral blood leukocytes. Serum concentrations of AFP in the patients ranged from less than 5 to 10,138 ng/ml. Nucleotide sequence was determined by direct sequencing using a single-stranded DNA template that was produced first through the polymerase chain reaction (PCR) amplification and then asymmetric PCR. In one HCC tissue taken from the patient with a high concentration of serum AFP, nucleotides different from published ones were detected at -120 and -113. These changes, however, probably reflect a DNA polymorphism, because peripheral blood leukocytes of the same patient had the same changes. Including this patient, no mutations in the region from -160 to -10 were detected in the HCC specimens we have examined. These results suggest that the extremely proximal promoter region of the AFP gene where glucocorticoid-responsive element and HNF-1 binding sites exist is not responsible for the re-expression of AFP in HCC.

Adult↗

PubMed1994

A right lower abdominal mass due to Yersinia mesenteric lymphadenitis.

We report the case of a 14-year-old female with Yersinia mesenteric lymphadenitis presenting as a right lower abdominal mass. Although such cases are very rare, Yersinia infection should be considered in the differential diagnosis of a right lower abdominal mass.

Adolescent↗

PubMed1994

Hepatitis C viral markers in patients who received blood that was positive for hepatitis C virus core antibody, with genetic evidence of hepatitis C virus transmission.

BACKGROUND: Despite the use of the anti-c100-3 assay for blood donor screening, posttransfusion non-A,non-B hepatitis still occurred. A more sensitive assay should be developed to prevent this. STUDY DESIGN AND METHODS: Stored serum specimens from 2020 healthy blood donors who were negative for c100-3 antibody to hepatitis C virus (HCV) were retrospectively screened for the presence of antibodies against a core protein of HCV using an enzyme-linked immunosorbent assay and Western blot analysis as part of a study on posttransfusion non-A,non-B hepatitis. RESULTS: Eight (0.4%) of the 2020 donors were positive for HCV core antibody. Posttransfusion non-A,non-B hepatitis occurred in 5 of five patients known to have received blood that was positive for HCV core antibody and 1 of 141 patients transfused with blood that was negative for HCV core antibody. The total incidence of posttransfusion non-A,non-B hepatitis was 4.1 percent (6/146). The nucleotide sequence of the nonstructural 5 region of the HCV genome obtained from two donors and corresponding recipients was also analyzed. The HCV genome sequences were identical for one donor-recipient pair, and there was 99.4-percent homology for a second pair. CONCLUSION: Anti-core-positive blood proved to be highly infectious for HCV, and this validated the use of the second-generation anti-HCV assay for blood donor screening.

Base Sequence↗

PubMed1994

[Primary biliary cirrhosis: symptoms, laboratory data and diagnosis].

The most frequent and important symptoms in primary biliary cirrhosis (PBC) are pruritus and jaundice. In the majority, jaundice appears within one half to two years of onset of pruritus. Xanthoma, bone change and sicca syndrome are often observed. The recent increase in number of asymptomatic PBC is the result of progagation of medical examination. In the biochemical tests, elevation of the biliary enzymes, such as ALP and gamma-GTP, is characteristic, as well as, a high level of serum IgM. Serum bilirubin values are gradually raised along with the clinical course of the disease. Positive antimitochondrial antibody (AMA) is the most valuable immunological finding for the diagnosis of PBC. Anti-pyruvate dehydrogenase complex E2 component E2 has the same significance as AMA. Diagnostic criteria si shown in this paper.

Humans↗

PubMed1993

Clinical evaluation of the antibody against core protein of hepatitis C virus.

The authors measured antibody against the core protein of hepatitis C virus (HCV) in patients with acute or chronic hepatitis and healthy blood donors, and compared the results with the one obtained from anti-C100-3 assay. To characterize this antibody (anti-core), we also examined the patients with past posttransfusional acute non-A, non-B hepatitis and investigated how frequently viraemia of HCV persisted after the acute phase of hepatitis detecting HCV RNA by polymerase chain reaction. Anti-core was detected in 109/128 (85.2%) of patients with chronic hepatitis and the detection rate of anti-C100-3 was 95/128 (74.2%), respectively. Twenty seven of 33 (82%) patients with past postransfusional acute hepatitis were still positive for anti-core concomitant with the presence of anti-C100-3, having accompanied the presence of HCV RNA in 24/33 (73%). Eight of 2,020 (0.4%) healthy blood donors who were negative for anti-C100-3 were anti-core-positive, and all 5 patients transfused with this anti-core positive blood suffered from posttransfusion hepatitis C. Thus, anti-core antibody was closely associated with the presence of HCV RNA and considered to be a reliable marker of the virus replication.

Antigens, Viral↗

PubMed1993

Double-barrelled tubular duplication of the ileum.

A three year old boy with a 10 cm double-barrelled tubular duplication of the distal ileum is reported. He presented with a small bowel obstruction after a large meal of mandarin oranges. At laparotomy an obstruction of both lumens was found which communicated at both ends with the normal ileal lumen. Although cystic duplications of the small intestine are common, tubular duplications are relatively rare, especially an obstruction with impacted undigested foods.

Child, Preschool↗

PubMed1993

Inhibition by recombinant SLPI and half-SLPI (Asn55-Ala107) of elastase and cathepsin G activities: consequence for neutrophil-platelet cooperation.

1. The capacity of recombinant human secretory leukocyte proteinase inhibitor (SLPI) to inhibit human leukocyte elastase (HLE) and cathepsin G (Cat G) was investigated and compared with a recombinant truncated form (carboxyl-terminal domain, Asn55-Ala107) called 1/2 SLPI. 2. Both compounds were efficient when tested against enzymatic activities of purified HLE and Cat G indicating that the HLE- and Cat G-inhibitory sites were preserved in the truncated form. SLPI and 1/2 SLPI also affected platelet activation induced by 0.2 microM Cat G (IC50 = 112 +/- 13 nM for SLPI and 280 +/- 12 nM for 1/2 SLPI). 3. The effects of SLPI and 1/2 SLPI were then tested against polymorphonuclear neutrophil (PMN)-mediated platelet activation, a cell-to-cell interaction mediated by HLE and Cat G released from PMN. In this experimental system, addition of SLPI or 1/2 SLPI before N-formyl-Met-Leu-Phe (fMLP) led to the inhibition of the resulting platelet activation. As was the case for Cat G enzymatic activity and Cat G-induced platelet activation, SLPI was more efficient than 1/2 SLPI (IC50 = 676 +/- 69 nM vs 1121 +/- 150 nM). 4. The ratio of the IC50 against PMN-mediated platelet activation compared to purified Cat G-mediated platelet activation was 6.03 for SLPI and 4.32 for 1/2 SLPI. This difference may be due to the smaller size of the truncated form which could allow this molecule to diffuse more easily between PMN and platelets. 5. In conclusion, 1/2 SLPI could be a promising candidate in the treatment of pathological states linked to inflammation in which participation of HLE and Cat G has been evoked.

Amino Acid Sequence↗

PubMed1993

Left ventricular wall thickness in normal mongrel dogs.

To clarify the normal value of ventricular wall thickness we directly measured the ventricular wall thickness of 50 normal mongrel dogs of one year old. Because of a wide range in body weight from 6.0 to 16.0 kg of these 50 dogs, we selected 34 dogs weighing 8 to 12 kg to calculate the mean ventricular wall thickness as normal value of one year old. The results obtained were as follows; (1) The mean and standard deviation of the left ventricular wall thickness was 7.1 +/- 1.2 mm at anterior, 6.3 +/- 1.6 mm at posterior, 7.1 +/- 1.3 mm at lateral, 10.3 +/- 1.8 mm at the interventricular septum, and that of the right ventricular wall thickness was 3.4 +/- 1.0 mm. (2) Although any site of the ventricular wall thickness correlated significantly to heart weight, only the anterior left ventricular wall and interventricular septum barely correlated to body weight. (3) There was no significant correlation between arterial blood pressure and the ventricular wall thickness. Further study should be necessary to clarify influences of aging on the ventricular thickness and to determine the criteria of ventricular hypertrophy.

Alanine Transaminase↗

PubMed1993

Assessment of pulmonary edema based on extravascular thermal volume in dogs.

To establish criteria of pulmonary edema by extravascular thermal volume (ETV), ETV and a roentgenogram of the thorax were compared in normal and experimental hydrostatic pulmonary edema dogs. ETV was measured by the double indicator dilution technique using heat as a diffusible indicator and sodium ions as a non-diffusible indicator (thermal-Na method). Mean ETV in 14 dogs under physiologic conditions was 8.20 +/- 1.44 ml/kg. Comparison of ETV with the roentgenogram indicated the density of thoracic the roentgenogram to increase when ETV exceeded 11 ml/kg. Pulmonary edema was recognized clearly in the thoracic roentgenogram at more than 15 ml/kg of ETV. Further increase in ETV did not occur with additional radiographic change. ETV was significantly (P < 0.01) correlated with arterial oxygen tension (PaO2) but not statistically correlated with colloid oncotic pressure (COP), pulmonary arterial wedge pressure (PAWP) or PAWP-COP. Measurement of ETV would thus, appear to be a reliable method for evaluating the severity of pulmonary edema, which has been difficult to diagnose by roentgenography and should facilitate the early diagnosis and management of pulmonary edema.

Animals↗

PubMed1993

Animal pharmacokinetics of FK037, a novel parenteral broad-spectrum cephalosporin.

Single-dose pharmacokinetics of FK037 has been investigated in laboratory animals. After bolus intravenous dosing with 20 mg/kg, the elimination half-life of FK037 varied in the species; with values of 0.27, 0.30, 0.97, 1.29 and 1.76 hours in mice, rats, rabbits, dogs and monkeys, respectively. The volume of distribution ranged between 260 ml/kg in rats and 390 ml/kg in dogs. These parameters approximated those of ceftazidime and cefpirome used as reference drugs. The renal clearance of FK037 was almost equal to glomerular filtration rate (GFR) in rabbits. Probenecid did not affect the elimination half-life of FK037 and its clearance ratio to GFR. These findings suggest that FK037 is solely excreted by glomerular filtration. FK037 readily penetrated into the tissues and inflammatory exudate fluid in rats, and the tissue level was highest in the kidneys, and decreased in the following order; lungs > heart > liver > spleen. Penetration of FK037, cefpirome and ceftazidime into the cerebrospinal fluid were determined using induced staphylococcal meningitis in rabbits. The penetration percentage ranged from 14.2 to 16.0% for these drugs with no significant differences. The major route of excretion of FK037 was via the kidney, with more than 74% of the dose being excreted in the urine within 24 hours after dosing to each species. Biliary excretion was low, 0.79% in rats. Bioautograms showed only unchanged drug in the plasma, urine and bile. Serum protein binding was low (8.8 to 17.6%) in all the species studied.

Animals↗

PubMed1993

FK037, a new parenteral cephalosporin with a broad antibacterial spectrum: synthesis and antibacterial activity.

Explore the source record for details and available documents.

Bacteria↗

PubMed1993

In vitro antibacterial activity of FK037, a novel parenteral broad-spectrum cephalosporin.

FK037 is a new parenteral cephalosporin, which offers some advantages over the commercially available parenteral cephalosporins. It demonstrated potent broad-spectrum activity against clinical isolates of Gram-positive bacteria including methicillin-resistant staphylococci, and Gram-negative bacteria including Pseudomonas aeruginosa. Against clinical isolates of aerobic Gram-positive bacteria, FK037, like cefpirome, demonstrated more potent activity than ceftazidime, cefoperazone and ceftizoxime. It is noteworthy that FK037, on the basis of the MIC90s, was the most active of all the cephalosporins tested against methicillin-resistant Staphylococcus aureus (MRSA). It was similar in activity to cefpirome against methicillin-sensitive S. aureus (MSSA). Against clinical isolates of aerobic Gram-negative bacteria, FK037, like cefpirome, was superior to cefoperazone, similar to ceftazidime and inferior to ceftizoxime in activity. Against P. aeruginosa, FK037 was superior to cefoperazone, similar or slightly superior to cefpirome and inferior to ceftazidime in activity. However, FK037 exhibited significant activity against Citrobacter and Enterobacter which were highly resistant to ceftazidime, cefoperazone and ceftizoxime. FK037 had an advantage in that its bactericidal activity against S. aureus, Escherichia coli and P. aeruginosa at sub-MICs (1/2 or 1/4 the MIC) was much stronger than those of cefpirome and ceftazidime. Moreover, it exhibited potent bactericidal activity against MSSA, MRSA and P. aeruginosa in a pharmacokinetic in vitro model simulating human plasma concentrations after intravenous dosage of 0.125, 1.0 and 1.0 g, respectively. FK037 inhibited essential penicillin-binding proteins (PBPs), 1, 2 and 3 of S. aureus with a 50% inhibitory concentration (I50) of 0.58 micrograms/ml or lower. Of essential PBPs 3, 1a and 1b of E. coli and P. aeruginosa, FK037 inhibited PBP 3 at the lowest I50 (0.03 and 0.04 micrograms/ml, respectively) and PBPs 1a and 1b with I50 values of 2.7 micrograms/ml or lower. FK037, like cefpirome, was highly stable to hydrolysis by various beta-lactamases except Ic cephalosporinase from Bacteroides fragilis, and had extremely low affinity for beta-lactamases. Therefore, FK037 was more potent than ceftazidime in activity against beta-lactamase-producing bacteria except P. aeruginosa and Serratia marcescens. The ability of FK037 to penetrate the outer membrane of E. coli was slightly higher than that of ceftazidime, but slightly lower than that of cefpirome.

Anti-Bacterial Agents↗

PubMed1993

In vivo antibacterial activity of FK037, a novel parenteral broad-spectrum cephalosporin.

FK037 has potent therapeutic activity against lethal systemic infections and experimental local infections due to a wide variety of Gram-positive and Gram-negative bacteria such as staphylococci, Streptococcus pneumoniae, Enterobacteriaceae and Pseudomonas aeruginosa in mice. In murine systemic infections, FK037 was the most effective of the cephalosporins and imipenem tested against highly methicillin-resistant Staphylococcus aureus (H-MRSA). It was more effective than ceftazidime against selected strains of S. aureus and Enterobacteriaceae, except Serratia marcescens and P. aeruginosa against which FK037 was as effective as ceftazidime and was as effective as cefpirome against all organisms tested, except MRSA and P. aeruginosa against which FK037 was more effective than cefpirome. These results correlated well with its in vitro activity. In murine local infections, with few exceptions, FK037 was more effective than ceftazidime and cefpirome against Klebsiella pneumonia in ED50 values and against methicillin-sensitive S. aureus (MSSA) subcutaneous abscess, pyelonephritis with Staphylococcus epidermidis, E. coli and P. aeruginosa, intrauterine infections with S. aureus and E. coli in reducing the number of viable bacteria in the abscess, kidneys and uterus. It is noteworthy that the therapeutic effects of FK037 were more potent than had been anticipated from its in vitro activity against local infections with staphylococci and P. aeruginosa when compared with ceftazidime or cefpirome. In addition, the therapeutic effects of FK037 were equipotent or superior to those of cefpirome and ceftazidime against pneumonia due to MSSA, K. pneumoniae and P. aeruginosa in reducing the number of viable bacteria in the lungs in mice using an in vivo pharmacokinetic model simulating human plasma concentrations after drip infusion of usual clinical doses (0.25 to 1.0 g for MSSA, 0.063 to 0.125 g for K. pneumoniae and 1.0 to 2.0 g for P. aeruginosa). FK037 induced an in vivo post-antibiotic effect (PAE) of 3.4 hours against a thigh infection with MSSA in neutropenic mice. These results strongly suggest that it has potential for clinical use against various infections due to bacteria which include staphylococci and P. aeruginosa.

Abscess↗